Staff directory Víctor F. Puntes

Víctor F. Puntes

ICREA Research Professor and Group Leader
Vall d'Hebrón Institut de Recerca (VHIR)
Inorganic Nanoparticles



  • Antibody cooperative adsorption onto AuNPs and its exploitation to force natural killer cells to kill HIV-infected T cells

    Astorga-Gamaza A., Vitali M., Borrajo M.L., Suárez-López R., Jaime C., Bastus N., Serra-Peinado C., Luque-Ballesteros L., Blanch-Lombarte O., Prado J.G., Lorente J., Pumarola F., Pellicer M., Falcó V., Genescà M., Puntes V., Buzon M.J. Nano Today; 36 (101056) 2021. 10.1016/j.nantod.2020.101056. IF: 20.722

    HIV represents a persistent infection which negatively alters the immune system. New tools to reinvigorate different immune cell populations to impact HIV are needed. Herein, a novel nanotool for the specific enhancement of the natural killer (NK) immune response towards HIV-infected T-cells has been developed. Bispecific Au nanoparticles (BiAb-AuNPs), dually conjugated with IgG anti-HIVgp120 and IgG anti-human CD16 antibodies, were generated by a new controlled, linker-free and cooperative conjugation method promoting the ordered distribution and segregation of antibodies in domains. The cooperatively-adsorbed antibodies fully retained the capabilities to recognize their cognate antigen and were able to significantly enhance cell-to-cell contact between HIV-expressing cells and NK cells. As a consequence, the BiAb-AuNPs triggered a potent cytotoxic response against HIV-infected cells in blood and human tonsil explants. Remarkably, the BiAb-AuNPs were able to significantly reduce latent HIV infection after viral reactivation in a primary cell model of HIV latency. This novel molecularly-targeted strategy using a bispecific nanotool to enhance the immune system represents a new approximation with potential applications beyond HIV. © 2020 The Authors

  • Cerium oxide nanoparticles: A new therapeutic tool in liver diseases

    Casals G., Perramón M., Casals E., Portolés I., Fernández-Varo G., Morales-Ruiz M., Puntes V., Jiménez W. Antioxidants; 10 (5, 660) 2021. 10.3390/antiox10050660. IF: 6.313

    Oxidative stress induced by the overproduction of free radicals or reactive oxygen species (ROS) has been considered as a key pathogenic mechanism contributing to the initiation and progression of injury in liver diseases. Consequently, during the last few years antioxidant substances, such as superoxide dismutase (SOD), resveratrol, colchicine, eugenol, and vitamins E and C have received increasing interest as potential therapeutic agents in chronic liver diseases. These substances have demonstrated their efficacy in equilibrating hepatic ROS metabolism and thereby improving liver functionality. However, many of these agents have not successfully passed the scrutiny of clinical trials for the prevention and treatment of various diseases, mainly due to their unspecificity and consequent uncontrolled side effects, since a minimal level of ROS is needed for normal functioning. Recently, cerium oxide nanoparticles (CeO2 NPs) have emerged as a new powerful antioxidant agent with therapeutic properties in experimental liver disease. CeO2 NPs have been reported to act as a ROS and reactive nitrogen species (RNS) scavenger and to have multi-enzyme mimetic activity, including SOD activity (deprotionation of superoxide anion into oxygen and hydrogen peroxide), catalase activity (conversion of hydrogen peroxide into oxygen and water), and peroxidase activity (reducing hydrogen peroxide into hydroxyl radicals). Consequently, the beneficial effects of CeO2 NPs treatment have been reported in many different medical fields other than hepatology, including neurology, ophthalmology, cardiology, and oncology. Unlike other antioxidants, CeO2 NPs are only active at pathogenic levels of ROS, being inert and innocuous in healthy cells. In the current article, we review the potential of CeO2 NPs in several experimental models of liver disease and their safety as a therapeutic agent in humans as well. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

  • Formation and evolution of the nanoparticle environmental corona: The case of Au and humic acid

    Barbero F., Mayall C., Drobne D., Saiz-Poseu J., Bastús N.G., Puntes V. Science of the Total Environment; 768 (144792) 2021. 10.1016/j.scitotenv.2020.144792. IF: 7.963

    Studying the behaviour of nanomaterials after their release into natural water is essential to understand the risk associated to their environmental exposure. In particular, the interaction and adsorption of dissolved organic matter onto nanoparticles strongly influence the behaviour and fate of nanomaterials in natural water systems. We herein study the interaction of Au and Ag nanoparticles and humic acids, the principal component of natural dissolved organic matter. Physicochemical characterization results showed the formation of an organic matter corona, consisting of two layers: a “hard” one, firmly bound to the nanoparticle surface, and a “soft” one, in dynamic equilibrium and, consequently, highly dependent on the media organic matter concentration. The extent of the electro-steric stabilization of the so called environmental corona depends on the size of the supramolecular association of humic acid (which depends on its hydrophilic and lipophilic moieties), the nanoparticle size, the total concentration of organic matter in the media, and the ratio between them. Interestingly, environmental coronas can eventually prevent Ca2+ and Mg2+ induced aggregation at concentrations range present in most of the freshwater bodies. The humic coating formed on top of the Au or control Ag nanoparticles presented a similar profile, but the corrodibility of Ag led to a more natural detachment of the corona. These results were further confirmed by exposing the nanoparticles to a model of natural water and standard mud (LUFA 2.2 dispersion). In the latter case, after several days, nanoparticle sedimentation was observed, which was attributed to interactions with macro organic and inorganic matter (fraction larger than particulate matter). © 2021 Elsevier B.V.

  • Functional and morphological changes induced in mytilus hemocytes by selected nanoparticles

    Auguste M., Mayall C., Barbero F., Hočevar M., Alberti S., Grassi G., Puntes V.F., Drobne D., Canesi L. Nanomaterials; 11 (2, 470): 1 - 16. 2021. 10.3390/nano11020470. IF: 5.076

    Nanoparticles (NPs) show various properties depending on their composition, size, and surface coating, which shape their interactions with biological systems. In particular, NPs have been shown to interact with immune cells, that represent a sensitive surveillance system of external and internal stimuli. In this light, in vitro models represent useful tools for investigating nano-bio-interactions in immune cells of different organisms, including invertebrates. In this work, the effects of selected types of NPs with different core composition, size and functionalization (custom-made PVP-AuNP and commercial nanopolystyrenes PS-NH2 and PS-COOH) were investigated in the hemocytes of the marine bivalve Mytilus galloprovincialis. The role of exposure medium was evaluated using either artificial seawater (ASW) or hemolymph serum (HS). Hemocyte morphology was investigated by scanning electron microscopy (SEM) and different functional parameters (lysosomal membrane stability, phagocytosis, and lysozyme release) were evaluated. The results show distinct morphological and functional changes induced in mussel hemocytes depending on the NP type and exposure medium. Mussel hemocytes may represent a powerful alternative in vitro model for a rapid pre-screening strategy for NPs, whose utilization will contribute to the understanding of the possible impact of environmental exposure to NPs in marine invertebrates. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

  • Gold nanoparticles (AuNPs) impair LPS-driven immune responses by promoting a tolerogenic-like dendritic cell phenotype with altered endosomal structures

    Michelini S., Barbero F., Prinelli A., Steiner P., Weiss R., Verwanger T., Andosch A., Lütz-Meindl U., Puntes V.F., Drobne D., Duschl A., Horejs-Hoeck J. Nanoscale; 13 (16): 7648 - 7666. 2021. 10.1039/d0nr09153g. IF: 7.790

    Dendritic cells (DCs) shape immune responses by influencing T-cell activation. Thus, they are considered both an interesting model for studying nano-immune interactions and a promising target for nano-based biomedical applications. However, the accentuated ability of nanoparticles (NPs) to interact with biomolecules may have an impact on DC function that poses an unexpected risk of unbalanced immune reactions. Here, we investigated the potential effects of gold nanoparticles (AuNPs) on DC function and the consequences for effector and memory T-cell responses in the presence of the microbial inflammatory stimulus lipopolysaccharide (LPS). Overall, we found that, in the absence of LPS, none of the tested NPs induced a DC response. However, whereas 4-, 8-, and 11 nm AuNPs did not modulate LPS-dependent immune responses, 26 nm AuNPs shifted the phenotype of LPS-activated DCs toward a tolerogenic state, characterized by downregulation of CD86, IL-12 and IL-27, upregulation of ILT3, and induction of class E compartments. Moreover, this DC phenotype was less proficient in promoting Th1 activation and central memory T-cell proliferation. Taken together, these findings support the perception that AuNPs are safe under homeostatic conditions; however, particular care should be taken in patients experiencing a current infection or disorders of the immune system. © 2021 The Royal Society of Chemistry.

  • Gold nanoparticles coated with polyvinylpyrrolidone and sea urchin extracellular molecules induce transient immune activation

    Alijagic A., Barbero F., Gaglio D., Napodano E., Benada O., Kofroňová O., Puntes V.F., Bastús N.G., Pinsino A. Journal of Hazardous Materials; 402 (123793) 2021. 10.1016/j.jhazmat.2020.123793. IF: 10.588

    We report that the immunogenicity of colloidal gold nanoparticles coated with polyvinylpyrrolidone (PVP–AuNPs) in a model organism, the sea urchin Paracentrotus lividus, can function as a proxy for humans for in vitro immunological studies. To profile the immune recognition and interaction from exposure to PVP–AuNPs (1 and 10 μg mL−1), we applied an extensive nano-scale approach, including particle physicochemical characterisation involving immunology, cellular biology, and metabolomics. The interaction between PVP–AuNPs and soluble proteins of the sea urchin physiological coelomic fluid (blood equivalent) results in the formation of a protein “corona” surrounding the NPs from three major proteins that influence the hydrodynamic size and colloidal stability of the particle. At the lower concentration of PVP–AuNPs, the P. lividus phagocytes show a broad metabolic plasticity based on the biosynthesis of metabolites mediating inflammation and phagocytosis. At the higher concentration of PVP–AuNPs, phagocytes activate an immunological response involving Toll-like receptor 4 (TLR4) signalling pathway at 24 hours of exposure. These results emphasise that exposure to PVP–AuNPs drives inflammatory signalling by the phagocytes and the resolution at both the low and high concentrations of the PVP–AuNPs and provides more details regarding the immunogenicity of these NPs. © 2020 Elsevier B.V.

  • Growth-promoting gold nanoparticles decrease stress responses in arabidopsis seedlings

    Ferrari E., Barbero F., Busquets-Fité M., Franz-Wachtel M., Köhler H.-R., Puntes V., Kemmerling B. Nanomaterials; 11 (12, 3161) 2021. 10.3390/nano11123161. IF: 5.076

    The global economic success of man-made nanoscale materials has led to a higher production rate and diversification of emission sources in the environment. For these reasons, novel nanosafety approaches to assess the environmental impact of engineered nanomaterials are required. While studying the potential toxicity of metal nanoparticles (NPs), we realized that gold nanoparticles (AuNPs) have a growth-promoting rather than a stress-inducing effect. In this study we established stable short-and long-term exposition systems for testing plant responses to NPs. Exposure of plants to moderate concentrations of AuNPs resulted in enhanced growth of the plants with longer primary roots, more and longer lateral roots and increased rosette diameter, and reduced oxidative stress responses elicited by the immune-stimulatory PAMP flg22. Our data did not reveal any detri-mental effects of AuNPs on plants but clearly showed positive effects on growth, presumably by their protective influence on oxidative stress responses. Differential transcriptomics and proteomics analyses revealed that oxidative stress responses are downregulated whereas growth-promoting genes/proteins are upregulated. These omics datasets after AuNP exposure can now be exploited to study the underlying molecular mechanisms of AuNP-induced growth-promotion. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

  • Immunomodulatory function of polyvinylpyrrolidone (Pvp)-functionalized gold nanoparticles in vibrio-stimulated sea urchin immune cells

    Alijagic A., Bonura A., Barbero F., Puntes V.F., Gervasi F., Pinsino A. Nanomaterials; 11 (10, 2646) 2021. 10.3390/nano11102646. IF: 5.076

    We investigated the role of the gold nanoparticles functionalized with polyvinylpyrrolidone (PVP–AuNPs) on the innate immune response against an acute infection caused by Vibrio anguillarum in an in vitro immunological nonmammalian next-generation model, the sea urchin Paracentrotus lividus. To profile the immunomodulatory function of PVP–AuNPs (0.1 μg mL−1) in sea urchin immune cells stimulated by Vibrio (10 μg mL−1) for 3 h, we focused on the baseline immunological state of the donor, and we analysed the topography, cellular metabolism, and expression of human cell surface antigens of the exposed cells, as well as the signalling leading the interaction between PVP–AuNPs and the Vibrio-stimulated cells. PVP–AuNPs are not able to silence the inflammatory signalling (TLR4/p38MAPK/NF-κB signalling) that involves the whole population of P. lividus immune cells exposed to Vibrio. However, our findings emphasise the ability of PVP–AuNPs to stimulate a subset of rare cells (defined here as Group 3) that express CD45 and CD14 antigens on their surface, which are known to be involved in immune cell maturation and macrophage activation in humans. Our evidence on how PVP–AuNPs may stimulate sea urchin immune cells represents an important starting point for planning new research work on the topic. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

  • In situ nanoremediation of soils and groundwaters from the nanoparticle's standpoint: A review

    Marcon L., Oliveras J., Puntes V.F. Science of the Total Environment; 791 (148324) 2021. 10.1016/j.scitotenv.2021.148324. IF: 7.963

    Anthropogenic pollution coming from industrial processes, agricultural practices and consumer products, results in the release of toxic substances into rural and urban environments. Once released, these chemicals migrate through the atmosphere and water, and find their way into matrices such as sediments and groundwaters, thus making large areas potentially uninhabitable. Common pollutants, including heavy metal(loid)s, radionuclides, aliphatic hydrocarbons and halogenated organics, are known to adversely affect physiological systems in animal species. Pollution can be cleaned up using techniques such as coagulation, reverse osmosis, oxidation and biological methods, among others. The use of nanoparticles (NPs) extends the range of available technologies and offers particular benefits, not only by degrading, transforming and immobilizing contaminants, but also by reaching inaccessible areas and promoting biotic degradation. The development of NPs is understandably heralded as an environmentally beneficial technology; however, it is only now that the ecological risks associated with their use are being evaluated. This review presents recent developments in the use of engineered NPs for the in situ remediation of two paramount environmental matrices: soils and groundwaters. Emphasis will be placed on (i) the successful applications of nano-objects for environmental cleanup, (ii) the potential safety implications caused by the challenging requirements of [high reactivity toward pollutants] vs. [none reactivity toward biota], with a thorough view on their transport and evolution in the matrix, and (iii) the perspectives on scientific and regulatory challenges. To this end, the most promising nanomaterials will be considered, including nanoscale zerovalent iron, nano-oxides and carbonaceous materials. The purpose of the present review is to give an overview of the development of nanoremediators since they appeared in the 2000s, from their chemical modifications, mechanism of action and environmental behavior to an understanding of the problematics (technical limitations, economic constraints and institutional precautionary approaches) that will drive their future full-scale applications. © 2021

  • Innate Memory Reprogramming by Gold Nanoparticles Depends on the Microbial Agents That Induce Memory

    Swartzwelter B.J., Michelini S., Frauenlob T., Barbero F., Verde A., De Luca A.C., Puntes V., Duschl A., Horejs-Hoeck J., Italiani P., Boraschi D. Frontiers in Immunology; 12 (751683) 2021. 10.3389/fimmu.2021.751683. IF: 7.561

    Innate immune memory, the ability of innate cells to react in a more protective way to secondary challenges, is induced by exposure to infectious and other exogeous and endogenous agents. Engineered nanoparticles are particulate exogenous agents that, as such, could trigger an inflammatory reaction in monocytes and macrophages and could therefore be also able to induce innate memory. Here, we have evaluated the capacity of engineered gold nanoparticles (AuNPs) to induce a memory response or to modulate the memory responses induced by microbial agents. Microbial agents used were in soluble vs. particulate form (MDP and the gram-positive bacteria Staphylococcus aureus; β-glucan and the β-glucan-producing fungi C. albicans), and as whole microrganisms that were either killed (S. aureus, C. albicans) or viable (the gram-negative bacteria Helicobacter pylori). The memory response was assessed in vitro, by exposing human primary monocytes from 2-7 individual donors to microbial agents with or without AuNPs (primary response), then resting them for 6 days to allow return to baseline, and eventually challenging them with LPS (secondary memory response). Primary and memory responses were tested as production of the innate/inflammatory cytokine TNFα and other inflammatory and anti-inflammatory factors. While inactive on the response induced by soluble microbial stimuli (muramyl dipeptide -MDP-, β-glucan), AuNPs partially reduced the primary response induced by whole microorganisms. AuNPs were also unable to directly induce a memory response but could modulate stimulus-induced memory in a circumscribed fashion, limited to some agents and some cytokines. Thus, the MDP-induced tolerance in terms of TNFα production was further exacerbated by co-priming with AuNPs, resulting in a less inflammatory memory response. Conversely, the H. pylori-induced tolerance was downregulated by AuNPs only relative to the anti-inflammatory cytokine IL-10, which would lead to an overall more inflammatory memory response. These effects of AuNPs may depend on a differential interaction/association between the reactive particle surfaces and the microbial components and agents, which may lead to a change in the exposure profiles. As a general observation, however, the donor-to-donor variability in memory response profiles and reactivity to AuNPs was substantial, suggesting that innate memory depends on the individual history of exposures. © Copyright © 2021 Swartzwelter, Michelini, Frauenlob, Barbero, Verde, De Luca, Puntes, Duschl, Horejs-Hoeck, Italiani and Boraschi.

  • Interaction between macrophages and nanoparticles: In vitro 3d cultures for the realistic assessment of inflammatory activation and modulation of innate memory

    Swartzwelter B.J., Verde A., Rehak L., Madej M., Puntes V.F., De Luca A.C., Boraschi D., Italiani P. Nanomaterials; 11 (1, 207): 1 - 13. 2021. 10.3390/nano11010207. IF: 5.076

    Understanding the modes of interaction between human monocytes/macrophages and engineered nanoparticles is the basis for assessing particle safety, in terms of activation of innate/inflammatory reactions, and their possible exploitation for medical applications. In vitro assessment of nanoparticle-macrophage interaction allows for examining the response of primary human cells, but the conventional 2D cultures do not reproduce the three-dimensional spacing of a tissue and the interaction of macrophages with the extracellular tissue matrix, conditions that shape macrophage recognition capacity and reactivity. Here, we have compared traditional 2D cultures with cultures on a 3D collagen matrix for evaluating the capacity gold nanoparticles to induce monocyte activation and subsequent innate memory in human blood monocytes in comparison to bacterial LPS. Results show that monocytes react to stimuli almost in the same way in 2D and 3D cultures in terms of production of TNFα and IL-6, but that notable differences are found when IL-8 and IL-1Ra are examined, in particular in the recall/memory response of primed cells to a second stimulation, with the 3D cultures showing cell activation and memory effects of nanoparticles better. In addition, the response variations in monocytes/macrophages from different donors point towards a personalized assessment of the nanoparticle effects on macrophage activation. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

  • Interaction of nanoparticles with endotoxin Importance in nanosafety testing and exploitation for endotoxin binding

    Mangini M., Verde A., Boraschi D., Puntes V.F., Italiani P., De Luca A.C. Nanotoxicology; 15 (4): 558 - 576. 2021. 10.1080/17435390.2021.1898690. IF: 5.913

    The interaction between engineered nanoparticles and the bacterial lipopolysaccharide, or endotoxin, is an event that warrants attention. Endotoxin is one of the most potent stimulators of inflammation and immune reactions in human beings, and is a very common contaminant in research labs. In nanotoxicology and nanomedicine, the presence of endotoxin on the nanoparticle surface affects their biological properties leading to misinterpretation of results. This review discusses the importance of detecting the endotoxin contamination on nanoparticles, focusing on the current method of endotoxin detection and their suitability for nanoparticulate materials. Conversely, the capacity of nanoparticles to bind endotoxin can be enhanced by functionalization with endotoxin-capturing molecules, opening the way to the development of novel endotoxin detection assays. © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

  • Introducing visible-light sensitivity into photocatalytic CeO2nanoparticles by hybrid particle preparation exploiting plasmonic properties of gold: Enhanced photoelectrocatalysis exemplified for hydrogen peroxide sensing

    Zhao S., Riedel M., Patarroyo J., Bastus N., Puntes V., Yue Z., Lisdat F., Parak W.J. Nanoscale; 13 (2): 980 - 990. 2021. 10.1039/d0nr06356h. IF: 7.790

    In this report we combine the catalytic properties of CeO2 nanoparticles with their transduction ability for photoelectrochemical sensing. This study highlights the usage of CeO2 providing catalytic activity towards H2O2, but only with a limited excitation range in the UV for the construction of a sensing system. In order to improve the photoelectrocatalysis of CeO2 nanoparticles by extending their excitation to visible light, Au/CeO2 core/shell hybrid nanoparticles have been synthesized. The hybrid nanoparticles are fixed on electrodes, allowing for the generation of photocurrents, the direction of which can be controlled by the electrode potential (without bias). The application of the hybrid nanoparticles results in an enhanced photocurrent amplitude under white light illumination as compared to the pure CeO2 nanoparticles. Wavelength-dependent measurements confirm the participation of the Au core in the signal transduction. This can be explained by improved charge carrier generation within the hybrid particles. Thus, by using a plasmonic element the photoelectochemical response of a catalytic nanoparticle (i.e. CeO2) has been spectrally extended. The effect can be exploited for sensorial hydrogen peroxide detection. Here higher photocatalytic current responses have been found for the hybrid particles fixed to gold electrodes although the catalytic reduction has been comparable for both types of nanoparticles. Thus, it can be demonstrated that Au/CeO2 core-shell nanoparticles allow the utilization of visible light for photoelectrochemical hydrogen peroxide (H2O2) detection with improved sensitivity under white light illumination or application of such particles with only visible light excitation, which is not possible for pure CeO2. With help of the layer-by-layer (LbL) technique for nanoparticle immobilization, the electrode response can be adjusted and with a 5 layers electrode a low detection limit of about 3 μM H2O2 with a linear detection range up to 2000 μM is obtained. This journal is © The Royal Society of Chemistry.

  • Mesoporous silica coated CeO2nanozymes with combined lipid-lowering and antioxidant activity induce long-term improvement of the metabolic profile in obese Zucker rats

    Parra-Robert M., Zeng M., Shu Y., Fernández-Varo G., Perramón M., Desai D., Chen J., Guo D., Zhang X., Morales-Ruiz M., Rosenholm J.M., Jiménez W., Puntes V., Casals E., Casals G. Nanoscale; 13 (18): 8452 - 8466. 2021. 10.1039/d1nr00790d. IF: 7.790

    Obesity is one of the most important public health problems that is associated with an array of metabolic disorders linked to cardiovascular disease, stroke, type 2 diabetes, and cancer. A sustained therapeutic approach to stop the escalating prevalence of obesity and its associated metabolic comorbidities remains elusive. Herein, we developed a novel nanocomposite based on mesoporous silica coated cerium oxide (CeO2) nanozymes that reduce the circulating levels of fatty acids and remarkably improve the metabolic phenotype in a model of obese Zucker rats five weeks after its administration. Lipidomic and gene expression analyses showed an amelioration of the hyperlipidemia and of the hepatic and adipose metabolic dysregulations, which was associated with a down-regulation of the hepatic PI3K/mTOR/AKT pathway and a reduction of the M1 proinflammatory cytokine TNF-a. In addition, the coating of the CeO2 maximized its cell antioxidant protective effects and minimized non-hepatic biodistribution. The one-pot synthesis method for the nanocomposite fabrication is implemented entirely in aqueous solution, room temperature and open atmosphere conditions, favoring scalability and offering a safe and translatable lipid-lowering and antioxidant nanomedicine to treat metabolic comorbidities associated with obesity. This approach may be further applied to address other metabolic disorders related to hyperlipidemia, low-grade inflammation and oxidative stress. © 2021 The Royal Society of Chemistry.

  • Microfluidic In Vitro Platform for (Nano)Safety and (Nano)Drug Efficiency Screening

    Kohl Y., Biehl M., Spring S., Hesler M., Ogourtsov V., Todorovic M., Owen J., Elje E., Kopecka K., Moriones O.H., Bastús N.G., Simon P., Dubaj T., Rundén-Pran E., Puntes V., William N., von Briesen H., Wagner S., Kapur N., Mariussen E., Nelson A., Gabelova A., Dusinska M., Velten T., Knoll T. Small; 17 (15, 2006012) 2021. 10.1002/smll.202006012. IF: 13.281

    Microfluidic technology is a valuable tool for realizing more in vitro models capturing cellular and organ level responses for rapid and animal-free risk assessment of new chemicals and drugs. Microfluidic cell-based devices allow high-throughput screening and flexible automation while lowering costs and reagent consumption due to their miniaturization. There is a growing need for faster and animal-free approaches for drug development and safety assessment of chemicals (Registration, Evaluation, Authorisation and Restriction of Chemical Substances, REACH). The work presented describes a microfluidic platform for in vivo-like in vitro cell cultivation. It is equipped with a wafer-based silicon chip including integrated electrodes and a microcavity. A proof-of-concept using different relevant cell models shows its suitability for label-free assessment of cytotoxic effects. A miniaturized microscope within each module monitors cell morphology and proliferation. Electrodes integrated in the microfluidic channels allow the noninvasive monitoring of barrier integrity followed by a label-free assessment of cytotoxic effects. Each microfluidic cell cultivation module can be operated individually or be interconnected in a flexible way. The interconnection of the different modules aims at simulation of the whole-body exposure and response and can contribute to the replacement of animal testing in risk assessment studies in compliance with the 3Rs to replace, reduce, and refine animal experiments. © 2021 The Authors. Small published by Wiley-VCH GmbH

  • Pharmacokinetics, biodistribution, and biosafety of pegylated gold nanoparticles in vivo

    Kozics K., Sramkova M., Kopecka K., Begerova P., Manova A., Krivosikova Z., Sevcikova Z., Liskova A., Rollerova E., Dubaj T., Puntes V., Wsolova L., Simon P., Tulinska J., Gabelova A. Nanomaterials; 11 (7, 1702) 2021. 10.3390/nano11071702. IF: 5.076

    Despite the obvious advantages of gold nanoparticles for biomedical applications, controversial and incomplete toxicological data hamper their widespread use. Here, we present the results from an in vivo toxicity study using gold nanoparticles coated with polyethylene glycol (PEG-AuNPs). The pharmacokinetics and biodistribution of PEG-AuNPs were examined in the rat’s liver, lung, spleen, and kidney after a single i.v. injection (0.7 mg/kg) at different time intervals. PEG-AuNPs had a relatively long blood circulation time and accumulated primarily in the liver and spleen, where they remained for up to 28 days after administration. Increased cytoplasmic vacuolation in hepatocytes 24 h and 7 days after PEG-AuNPs exposure and apoptotic-like cells in white splenic pulp 24 h after administration has been detected, however, 28 days post-exposure were no longer observed. In contrast, at this time point, we identified significant changes in lipid metabolism, altered levels of liver injury markers, and elevated monocyte count, but without marked biological relevance. In blood cells, no DNA damage was present in any of the studied time intervals, with the exception of DNA breakage transiently detected in primary kidney cells 4 h post-injection. Our results indicate that the tissue accumulation of PEG-AuNPs might result in late toxic effects. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

  • Preclinical studies conducted on nanozyme antioxidants: Shortcomings and challenges based on US FDA regulations

    Ghorbani M., Izadi Z., Jafari S., Casals E., Rezaei F., Aliabadi A., Moore A., Ansari A., Puntes V., Jaymand M., Derakhshankhah H. Nanomedicine; 16 (13): 1133 - 1151. 2021. 10.2217/nnm-2021-0030. IF: 5.307

    The wide prevalence of oxidative stress-induced diseases has led to a growing demand for antioxidant therapeutics worldwide. Nanozyme antioxidants are drawing enormous attention as practical alternatives for conventional antioxidants. The considerable body of research over the last decade and the promising results achieved signify the potential of nanozyme antioxidants to secure a place in the expanding market of antioxidant therapeutics. Nonetheless, there is no report on clinical trials for their further evaluation. Through analyzing in-depth selected papers which have conducted in vivo studies on nanozyme antioxidants, this review aims to pinpoint and discuss possible reasons impeding development of research toward clinical studies and to offer some practical solutions for future studies to bridge the gap between preclinical and clinical stages. "We did not experience these kinds of strange illnesses in the past." Everybody might have heard such a familiar sentence from their grandparents and asked themselves, why? The current paper aims to provide readers with one of the answers: "Oxidative stress", which happens when the body fails to neutralize damage caused by unstable molecules called free radicals. In this paper, the authors present the seriousness of oxidative stress-induced clinical conditions. They discuss one of the promising treatments, nanozyme antioxidants, these are mostly based on nano-sized materials with enzyme-like function, in other words, they can speed up chemical reactions. Despite significant results, nanozyme antioxidants have not been investigated in clinical studies. This paper intends to search for the main reasons for this and suggest possible solutions. © 2021 Future Medicine Ltd. © 2021 Future Medicine Ltd.. All rights reserved.

  • Scalable synthesis of multicomponent multifunctional inorganic core@mesoporous silica shell nanocomposites

    Zeng M., Shu Y., Parra-Robert M., Desai D., Zhou H., Li Q., Rong Z., Karaman D.Ş., Yang H., Peng J., Fernandez-Varo G., Jiménez W., Casals G., Puntes V., Rosenholm J.M., Casals E. Materials science & engineering. C, Materials for biological applications; 128: 112272. 2021. 10.1016/j.msec.2021.112272. IF: 7.328

    Integrating multiple materials with different functionalities in a single nanostructure enables advances in many scientific and technological applications. However, such highly sophisticated nanomaterials usually require complex synthesis processes that complicate their preparation in a sustainable and industrially feasible manner. Herein, we designed a simple general method to grow a mesoporous silica shell onto any combination of hydrophilic nanoparticle cores. The synthetic strategy, based on the adjustment of the key parameters of the sol-gel process for the silica shell formation, allows for the embedment of single, double, and triple inorganic nanoparticles within the same shell, as well as the size-control of the obtained nanocomposites. No additional interfacial adhesive layer is required on the nanoparticle surfaces for the embedding process. Adopting this approach, electrostatically stabilized, small-sized (from 4 to 15 nm) CeO2, Fe3O4, Gd2O3, NaYF4, Au, and Ag cores were used to test the methodology. The mean diameter of the resulting nanocomposites could be as low as 55 nm, with high monodispersity. These are very feasible sizes for biological intervention, and we further observed increased nanoparticle stability in physiological environments. As a demonstration of their increased activity as a result of this, the antioxidant activity of CeO2 cores was enhanced when in core-shell form. Remarkably, the method is conducted entirely at room temperature, atmospheric conditions, and in aqueous solvent with the use of ethanol as co-solvent. These facile and even "green" synthesis conditions favor scalability and easy preparation of multicomponent nanocomposite libraries with standard laboratory glassware and simple benchtop chemistry, through this sustainable and cost-effective fabrication process. Copyright © 2021 Elsevier B.V. All rights reserved.

  • Stressor‐dependant changes in immune parameters in the terrestrial isopod crustacean, porcellio scaber: A focus on nanomaterials

    Mayall C., Dolar A., Kokalj A.J., Novak S., Razinger J., Barbero F., Puntes V., Drobne D. Nanomaterials; 11 (4, 934) 2021. 10.3390/nano11040934. IF: 5.076

    We compared the changes of selected immune parameters of Porcellio scaber to different stressors. The animals were either fed for two weeks with Au nanoparticles (NPs), CeO2 NPs, or Au ions or body‐injected with Au NPs, CeO2 NPs, or lipopolysaccharide endotoxin. Contrary to expec-tations, the feeding experiment showed that both NPs caused a significant increase in the total hae-mocyte count (THC). In contrast, the ion‐positive control resulted in a significantly decreased THC. Additionally, changes in phenoloxidase (PO)‐like activity, haemocyte viability, and nitric oxide (NO) levels seemed to depend on the stressor. Injection experiments also showed stressor‐depend-ant changes in measured parameters, such as CeO2 NPs and lipopolysaccharide endotoxin (LPS), caused more significant responses than Au NPs. These results show that feeding and injection of NPs caused an immune response and that the response differed significantly, depending on the exposure route. We did not expect the response to ingested NPs, due to the low exposure concentrations (100 μg/g dry weight food) and a firm gut epithelia, along with a lack of phagocytosis in the digestive system, which would theoretically prevent NPs from crossing the biological barrier. It remains a challenge for future research to reveal what the physiological and ecological significance is for the organism to sense and respond, via the immune system, to ingested foreign material. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

  • Sustained effect of zero-valent iron nanoparticles under semi-continuous anaerobic digestion of sewage sludge: Evolution of nanoparticles and microbial community dynamics

    Barrena R., Vargas-García M.D.C., Capell G., Barańska M., Puntes V., Moral-Vico J., Sánchez A., Font X. Science of the Total Environment; 777 (145969) 2021. 10.1016/j.scitotenv.2021.145969. IF: 7.963

    The effects of adding zero-valent iron nanoparticles (nZVI) on the physicochemical, biological and biochemical responses of a semi-continuous anaerobic digestion of sewage sludge have been assessed. Two sets of consecutive experiments of 103 and 116 days, respectively, were carried out in triplicate. nZVI were magnetically retained in the reactors, and the effect of punctual doses (from 0.27 to 4.33 g L−1) over time was studied. Among the different parameters monitored, only methane content in the biogas was significantly higher when nZVI was added. However, this effect was progressively lost after the addition, and in 5–7 days, the methane content returned to initial values. The increase in the oxidation state of nanoparticles seems to be related to the loss of effect over time. Higher dose (4.33 g L−1) sustained positive effects for a longer time along with higher methane content, but this fact seems to be related to microbiome acclimation. Changes in microbial community structure could also play a role in the mechanisms involved in methane enhancement. In this sense, the microbial consortium analysis reported a shift in the balance among acetogenic eubacterial communities, and a marked increase in the relative abundance of members assigned to Methanothrix genus, recognized as acetoclastic species showing high affinity for acetate, which explain the rise in methane content in the biogas. This research demonstrates that biogas methane enrichment in semicontinuous anaerobic digesters can be achieved by using nZVI nanoparticles, thus increasing energy production or reducing costs of a later biogas upgrading process. © 2021 Elsevier B.V.

  • The interactions between nanoparticles and the innate immune system from a nanotechnologist perspective

    Ernst L.M., Casals E., Italiani P., Boraschi D., Puntes V. Nanomaterials; 11 (11, 2991) 2021. 10.3390/nano11112991. IF: 5.076

    The immune system contributes to maintaining the body’s functional integrity through its two main functions: recognizing and destroying foreign external agents (invading microorganisms) and identifying and eliminating senescent cells and damaged or abnormal endogenous entities (such as cellular debris or misfolded/degraded proteins). Accordingly, the immune system can detect molecular and cellular structures with a spatial resolution of a few nm, which allows for detecting molecular patterns expressed in a great variety of pathogens, including viral and bacterial proteins and bacterial nucleic acid sequences. Such patterns are also expressed in abnormal cells. In this context, it is expected that nanostructured materials in the size range of proteins, protein aggregates, and viruses with different molecular coatings can engage in a sophisticated interaction with the immune system. Nanoparticles can be recognized or passed undetected by the immune system. Once detected, they can be tolerated or induce defensive (inflammatory) or anti-inflammatory responses. This paper describes the different modes of interaction between nanoparticles, especially inorganic nanoparticles, and the immune system, especially the innate immune system. This perspective should help to propose a set of selection rules for nanosafety-by-design and medical nanoparticle design. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.


  • A lab-on-a-chip system with an embedded porous membrane-based impedance biosensor array for nanoparticle risk assessment on placental Bewo trophoblast cells

    Schuller P., Rothbauer M., Kratz S.R.A., Höll G., Taus P., Schinnerl M., Genser J., Bastus N., Moriones O.H., Puntes V., Huppertz B., Siwetz M., Wanzenböck H., Ertl P. Sensors and Actuators, B: Chemical; 312 (127946) 2020. 10.1016/j.snb.2020.127946. IF: 7.100

    The human placenta is a unique organ serving as the lung, gut, liver, and kidney of the fetus, mediating the exchange of different endogenous as well as exogenous substances and gases between the mother and fetus during pregnancy. Additionally, the placental barrier protects the fetus from a range of environmental toxins, bacterial and viral infections, since any contaminant bridging the placenta may have unforeseeable effects on embryonal and fetal development. A more recent concern in placenta research, however, involves the ability of engineered nanoparticles to cross the placental barrier and/or affect its barrier function. To advance nanoparticle risk assessment at the human placental barrier, we have developed as proof-of-principle a highly integrated placenta-on-a-chip system containing embedded membrane-bound impedance microsensor arrays capable of non-invasively monitoring placental barrier integrity. Barrier integrity is continuously and label-free evaluated using porous membrane-based interdigitated electrode structures located on top of a porous PET membrane supporting a barrier of trophoblast-derived BeWo cell barrier in the absence and presence of standardized silicon dioxide (SiO2), titanium dioxide (TiO2), and zinc oxide (ZnO) nanomaterials. © 2020 Elsevier B.V.

  • Addressing Nanomaterial Immunosafety by Evaluating Innate Immunity across Living Species

    Boraschi D., Alijagic A., Auguste M., Barbero F., Ferrari E., Hernadi S., Mayall C., Michelini S., Navarro Pacheco N.I., Prinelli A., Swart E., Swartzwelter B.J., Bastús N.G., Canesi L., Drobne D., Duschl A., Ewart M.-A., Horejs-Hoeck J., Italiani P., Kemmerling B., Kille P., Prochazkova P., Puntes V.F., Spurgeon D.J., Svendsen C., Wilde C.J., Pinsino A. Small; 16 (21, 2000598) 2020. 10.1002/smll.202000598. IF: 11.459

    The interaction of a living organism with external foreign agents is a central issue for its survival and adaptation to the environment. Nanosafety should be considered within this perspective, and it should be examined that how different organisms interact with engineered nanomaterials (NM) by either mounting a defensive response or by physiologically adapting to them. Herein, the interaction of NM with one of the major biological systems deputed to recognition of and response to foreign challenges, i.e., the immune system, is specifically addressed. The main focus is innate immunity, the only type of immunity in plants, invertebrates, and lower vertebrates, and that coexists with adaptive immunity in higher vertebrates. Because of their presence in the majority of eukaryotic living organisms, innate immune responses can be viewed in a comparative context. In the majority of cases, the interaction of NM with living organisms results in innate immune reactions that eliminate the possible danger with mechanisms that do not lead to damage. While in some cases such interaction may lead to pathological consequences, in some other cases beneficial effects can be identified. © 2020 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

  • Bespoken Nanoceria: An Effective Treatment in Experimental Hepatocellular Carcinoma

    Fernández-Varo G., Perramón M., Carvajal S., Oró D., Casals E., Boix L., Oller L., Macías-Muñoz L., Marfà S., Casals G., Morales-Ruiz M., Casado P., Cutillas P.R., Bruix J., Navasa M., Fuster J., Garcia-Valdecasas J.C., Pavel M.C., Puntes V., Jiménez W. Hepatology; 72 (4): 1267 - 1282. 2020. 10.1002/hep.31139. IF: 14.679

    Background and Aims: Despite the availability of new-generation drugs, hepatocellular carcinoma (HCC) is still the third most frequent cause of cancer-related deaths worldwide. Cerium oxide nanoparticles (CeO2NPs) have emerged as an antioxidant agent in experimental liver disease because of their antioxidant, anti-inflammatory, and antisteatotic properties. In the present study, we aimed to elucidate the potential of CeO2NPs as therapeutic agents in HCC. Approach and Results: HCC was induced in 110 Wistar rats by intraperitoneal administration of diethylnitrosamine for 16 weeks. Animals were treated with vehicle or CeO2NPs at weeks 16 and 17. At the eighteenth week, nanoceria biodistribution was assessed by mass spectrometry (MS). The effect of CeO2NPs on tumor progression and animal survival was investigated. Hepatic tissue MS-based phosphoproteomics as well as analysis of principal lipid components were performed. The intracellular uptake of CeO2NPs by human ex vivo perfused livers and human hepatocytes was analyzed. Nanoceria was mainly accumulated in the liver, where it reduced macrophage infiltration and inflammatory gene expression. Nanoceria treatment increased liver apoptotic activity, while proliferation was attenuated. Phosphoproteomic analysis revealed that CeO2NPs affected the phosphorylation of proteins mainly related to cell adhesion and RNA splicing. CeO2NPs decreased phosphatidylcholine-derived arachidonic acid and reverted the HCC-induced increase of linoleic acid in several lipid components. Furthermore, CeO2NPs reduced serum alpha-protein levels and improved the survival of HCC rats. Nanoceria uptake by ex vivo perfused human livers and in vitro human hepatocytes was also demonstrated. Conclusions: These data indicate that CeO2NPs partially revert the cellular mechanisms involved in tumor progression and significantly increase survival in HCC rats, suggesting that they could be effective in patients with HCC. © 2020 The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of American Association for the Study of Liver Diseases.

  • Cerium Oxide Nanoparticles: Advances in Biodistribution, Toxicity, and Preclinical Exploration

    Casals E., Zeng M., Parra-Robert M., Fernández-Varo G., Morales-Ruiz M., Jiménez W., Puntes V., Casals G. Small; 16 (20, 1907322) 2020. 10.1002/smll.201907322. IF: 11.459

    Antioxidant nanoparticles have recently gained tremendous attention for their enormous potential in biomedicine. However, discrepant reports of either medical benefits or toxicity, and lack of reproducibility of many studies, generate uncertainties delaying their effective implementation. Herein, the case of cerium oxide is considered, a well-known catalyst in the petrochemistry industry and one of the first antioxidant nanoparticles proposed for medicine. Like other nanoparticles, it is now described as a promising therapeutic alternative, now as threatening to health. Sources of these discrepancies and how this analysis helps to overcome contradictions found for other nanoparticles are summarized and discussed. For the context of this analysis, what has been reported in the liver is reviewed, where many diseases are related to oxidative stress. Since well-dispersed nanoparticles passively accumulate in liver, it represents a major testing field for the study of new nanomedicines and their clinical translation. Even more, many contradictory works have reported in liver either cerium-oxide-associated toxicity or protection against oxidative stress and inflammation. Based on this, finally, the intention is to propose solutions to design improved nanoparticles that will work more precisely in medicine and safely in society. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

  • Epigenetics in breast cancer therapy—New strategies and future nanomedicine perspectives

    Buocikova V., Rios-Mondragon I., Pilalis E., Chatziioannou A., Miklikova S., Mego M., Pajuste K., Rucins M., Yamani N.E., Longhin E.M., Sobolev A., Freixanet M., Puntes V., Plotniece A., Dusinska M., Cimpan M.R., Gabelova A., Smolkova B. Cancers; 12 (12, 3622): 1 - 32. 2020. 10.3390/cancers12123622. IF: 6.126

    Epigenetic dysregulation has been recognized as a critical factor contributing to the development of resistance against standard chemotherapy and to breast cancer progression via epithelial-to-mesenchymal transition. Although the efficacy of the first-generation epigenetic drugs (epi-drugs) in solid tumor management has been disappointing, there is an increasing body of evidence showing that epigenome modulation, in synergy with other therapeutic approaches, could play an important role in cancer treatment, reversing acquired therapy resistance. However, the epigenetic therapy of solid malignancies is not straightforward. The emergence of nanotechnologies applied to medicine has brought new opportunities to advance the targeted delivery of epi-drugs while improving their stability and solubility, and minimizing off-target effects. Furthermore, the omics technologies, as powerful molecular epidemiology screening tools, enable new diagnostic and prognostic epigenetic biomarker identification, allowing for patient stratification and tailored management. In combination with new-generation epi-drugs, nanomedicine can help to overcome low therapeutic efficacy in treatment-resistant tumors. This review provides an overview of ongoing clinical trials focusing on combination therapies employing epi-drugs for breast cancer treatment and summarizes the latest nano-based targeted delivery approaches for epi-drugs. Moreover, it highlights the current limitations and obstacles associated with applying these experimental strategies in the clinics. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.

  • Gold Nanoparticles Modulate BCG-Induced Innate Immune Memory in Human Monocytes by Shifting the Memory Response towards Tolerance

    Benjamin J. Swartzwelter, Francesco Barbero, Alessandro Verde, Maria Mangini, Marinella Pirozzi, Anna Chiara De Luca, Victor F. Puntes, Luciana C. C. Leite, Paola Italiani, Diana Boraschi Cells; 9 (2, 284) 2020. 10.3390/cells9020284. IF: 4.366

  • Hepato(Geno)toxicity assessment of nanoparticles in a hepg2 liver spheroid model

    Elje E., Mariussen E., Moriones O.H., Bastús N.G., Puntes V., Kohl Y., Dusinska M., Rundén-Pran E. Nanomaterials; 10 (3, 545) 2020. 10.3390/nano10030545. IF: 4.324

    (1) In compliance with the 3Rs policy to reduce, refine and replace animal experiments, the development of advanced in vitro models is needed for nanotoxicity assessment. Cells cultivated in 3D resemble organ structures better than 2D cultures. This study aims to compare cytotoxic and genotoxic responses induced by titanium dioxide (TiO2), silver (Ag) and zinc oxide (ZnO) nanoparticles (NPs) in 2D monolayer and 3D spheroid cultures of HepG2 human liver cells. (2) NPs were characterized by electron microscopy, dynamic light scattering, laser Doppler anemometry, UV-vis spectroscopy and mass spectrometry. Cytotoxicity was investigated by the alamarBlue assay and confocal microscopy in HepG2 monolayer and spheroid cultures after 24 h of NP exposure. DNA damage (strand breaks and oxidized base lesions) was measured by the comet assay. (3) Ag-NPs were aggregated at 24 h, and a substantial part of the ZnO-NPs was dissolved in culture medium. Ag-NPs induced stronger cytotoxicity in 2D cultures (EC50 3.8 µg/cm2) than in 3D cultures (EC50 > 30 µg/cm2), and ZnO-NPs induced cytotoxicity to a similar extent in both models (EC50 10.1–16.2 µg/cm2). Ag-and ZnO-NPs showed a concentration-dependent genotoxic effect, but the effect was not statistically significant. TiO2-NPs showed no toxicity (EC50 > 75 µg/cm2). (4) This study shows that the HepG2 spheroid model is a promising advanced in vitro model for toxicity assessment of NPs. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.

  • Impact of Ag2S NPs on soil bacterial community – A terrestrial mesocosm approach

    Peixoto S., Khodaparast Z., Cornelis G., Lahive E., Green Etxabe A., Baccaro M., Papadiamantis A.G., Gonçalves S.F., Lynch I., Busquets-Fite M., Puntes V., Loureiro S., Henriques I. Ecotoxicology and Environmental Safety; 206 (111405) 2020. 10.1016/j.ecoenv.2020.111405. IF: 4.872

    Soils might be a final sink for Ag2S nanoparticles (NPs). Still, there are limited data on their effects on soil bacterial communities (SBC). To bridge this gap, we investigated the effects of Ag2S NPs (10 mg kg−1 soil) on the structure and function of SBC in a terrestrial indoor mesocosm, using a multi-species design. During 28 days of exposure, the SBC function-related parameters were analysed in terms of enzymatic activity, community level physiological profile, culture of functional bacterial groups [phosphorous-solubilizing bacteria (P-SB) and heterotrophic bacteria (HB)], and SBC structure was analysed by 16S rRNA gene-targeted denaturing gradient gel electrophoresis. The SBC exposed to Ag2S NPs showed a significative decrease of functional parameters, such as β-glucosidase activity and L-arginine consumption, and increase of the acid phosphatase activity. At the structural level, significantly lower richness and diversity were detected, but at later exposure times compared to the AgNO3 treatment, likely because of a low dissolution rate of Ag2S NPs. In fact, stronger effects were observed in soils spiked with AgNO3, in both functional and structural parameters. Changes in SBC structure seem to negatively correlate with parameters related to phosphorous (acid phosphatase activity) and carbon cycling (abundance of HB, P-SB, and β-glucosidase activity). Our results indicate a significant effect of Ag2S NPs on SBC, specifically on parameters related to carbon and phosphorous cycling, at doses as low as 10 mg kg-1 soil. These effects were only observed after 28 days, highlighting the importance of long-term exposure experiments for slowly dissolving NPs. © 2020 Elsevier Inc.

  • Increasing complexity of nanocrystals

    Bastús N.G., Gonzalez E., Puntes V. Nano Today; 32 (100859) 2020. 10.1016/j.nantod.2020.100859. IF: 16.907

    [No abstract available]

  • MOF-Beads Containing Inorganic Nanoparticles for the Simultaneous Removal of Multiple Heavy Metals from Water

    Boix G., Troyano J., Garzón-Tovar L., Camur C., Bermejo N., Yazdi A., Piella J., Bastus N.G., Puntes V.F., Imaz I., Maspoch D. ACS Applied Materials and Interfaces; 12 (9): 10554 - 10562. 2020. 10.1021/acsami.9b23206. IF: 8.758

    Pollution of water with heavy metals is a global environmental problem whose impact is especially severe in developing countries. Among water-purification methods, adsorption of heavy metals has proven to be simple, versatile, and cost-effective. However, there is still a need to develop adsorbents with a capacity to remove multiple metal pollutants from the same water sample. Herein, we report the complementary adsorption capacities of metal-organic frameworks (here, UiO-66 and UiO-66-(SH)2) and inorganic nanoparticles (iNPs; here, cerium-oxide NPs) into composite materials. These adsorbents, which are spherical microbeads generated in one step by continuous-flow spray-drying, efficiently and simultaneously remove multiple heavy metals from water, including As(III and V), Cd(II), Cr(III and VI), Cu(II), Pb(II), and Hg(II). We further show that these microbeads can be used as a packing material in a prototype of a continuous-flow water treatment system, in which they retain their metal-removal capacities upon regeneration with a gentle acidic treatment. As proof-of-concept, we evaluated these adsorbents for purification of laboratory water samples prepared to independently recapitulate each of two strongly polluted rivers: the Bone (Indonesia) and Buringanga (Bangladesh) rivers. In both cases, our microbeads reduced the levels of all the metal contaminants to below the corresponding permissible limits established by the World Health Organization (WHO). Moreover, we demonstrated the capacity of these microbeads to lower levels of Cr(VI) in a water sample collected from the Sarno River (Italy). Finally, to create adsorbents that could be magnetically recovered following their use in water purification, we extended our spray-drying technique to simultaneously incorporate two types of iNPs (CeO2 and Fe3O4) into UiO-66-(SH)2, obtaining CeO2/Fe3O4@UiO-66-(SH)2 microbeads that adsorb heavy metals and are magnetically responsive. Copyright © 2020 American Chemical Society.

  • Nanocrystal−molecular hybrids for the photocatalytic oxidation of water

    Bastús N.G., Gimbert-Suriñach C., Puntes V., Llobet A., Ventosa M., Oliveras J. ACS Applied Energy Materials; 3 (10): 10008 - 10014. 2020. 10.1021/acsaem.0c01685. IF: 4.473

    A modular molecular hybrid colloidal photocatalyst composed of TiO2 nanocrystals (TiO2-NCs) as a light absorber and the molecular complex [Ru(tda)(pypyr)2], Ru-tda, as a water oxidation catalyst precursor both anchored onto single-walled carbon nanotubes (SWCNTs) is described. This colloidal molecular hybrid photocatalyst, labeled as Ru-tda/SWCNT/TiO2-NCs, is a robust material that can be easily prepared and scaled up. At neutral pH, in the presence of 3 sun illumination, the molecular hybrid material Ru-tda/SWCNT/TiO2-NCs is capable of achieving the photocatalytic oxidation of water to dioxygen in the presence of persulfate, giving an unprecedented turnover number of 229. © 2020 American Chemical Society

  • Probing the immune responses to nanoparticles across environmental species. A perspective of the EU Horizon 2020 project PANDORA

    Pinsino A., Bastús N.G., Busquets-Fité M., Canesi L., Cesaroni P., Drobne D., Duschl A., Ewart M.-A., Gispert I., Horejs-Hoeck J., Italiani P., Kemmerling B., Kille P., Procházková P., Puntes V.F., Spurgeon D.J., Svendsen C., Wilde C.J., Boraschi D. Environmental Science: Nano; 7 (11): 3216 - 3232. 2020. 10.1039/d0en00732c. IF: 7.683

    Understanding how engineered nanomaterials affect immune responses of living organisms requires a strong collaborative effort between immunologists, toxicologists, ecologists, physiologists, inorganic chemists, nanomaterial scientists and experts in law and risk management. This perspective aims to provide a new viewpoint on the interaction between engineered nanomaterials and the immune defensive systems across living species, gained within the EU Horizon 2020 project PANDORA. We consider the effects of nanoparticle exposure on immune functions in plants, marine and terrestrial invertebrates and their relation to the current state of knowledge for vertebrates (in particular humans). These studies can shed light on the broader perspective of defensive and homeostatic mechanisms (immunity, inflammation, stress responses, microbiota, stem cell differentiation) suggesting ways to: i) perform a comparative analysis of the nanoparticle impact on immunity across model organisms; ii) inspire best practices in experimental methodologies for nanosafety/nanotoxicity studies; iii) regroup and harmonise fragmented research activities; iv) improve knowledge transfer strategies and nano-security; v) propose innovative tools and realistic solutions, thereby helping in identifying future research needs and tackling their challenges. This journal is © The Royal Society of Chemistry.

  • Simple spectroscopic determination of the hard protein corona composition in AuNPs: Albumin at 75%

    Vitali M., Casals E., Canals F., Colomé N., Puntes V. Nanoscale; 12 (29): 15832 - 15844. 2020. 10.1039/d0nr02379e. IF: 6.895

    We analyzed the different spectroscopic profiles of nanoparticle hard protein corona formation using two model proteins, albumin and immunoglobulin. When compared to serum, this served for the analysis of the hard protein corona main components. To do that, we employed time-resolved UV-Visible light absorption spectroscopy, dynamic light scattering, and zeta potential measurements during nanoparticle-protein incubation. Under the tested experimental conditions, the expected evolution from a non-stable (soft) to a stable (hard) protein corona was confirmed for serum and albumin. At the same time, immunoglobulin incubation inevitably failed to form a corona and led to nanoparticle aggregation. The formation profiles of the protein corona were similar in the case of albumin and serum, indicating the dominance of albumin coating the nanoparticle surface when exposed to plasma. This was confirmed by mass spectrometry. Chemical digestion of the nanoparticles bearing different protein coronas gave indications of the density of the different protein coatings. Overall, this study of the protein corona by determining the adsorption kinetics finger-print enables the development of precise nanotechnologies avoiding cumbersome processes and delaying proteomics analysis. This journal is © The Royal Society of Chemistry.

  • Understanding galvanic replacement reactions: the case of Pt and Ag

    Merkoçi F., Patarroyo J., Russo L., Piella J., Genç A., Arbiol J., Bastús N.G., Puntes V. Materials Today Advances; 5 (100037) 2020. 10.1016/j.mtadv.2019.100037. IF: 0.000

    Synthesis of nanocrystals (NCs), where material science elements are addressed with organic chemistry precision techniques, is especially challenging and difficult to control. This difficulty arises from the increased complexity of the mineralization processes and the generation of a liquid-solid interface. These aspects, along with a strong susceptibility to reaction kinetics, ultimately translate into serious challenges for reproducibility and morphological control. By systematically varying the different parameters used to control the morphology of NCs, including complexing agents, coreducers, and cooxidants, the general reaction landscape can be mapped and the most stable and reproducible recipes can be identified. We apply this concept to the model transmetallation reaction between immiscible Pt and Ag forming hollow Pt NCs by galvanic replacement reactions. In this work, 648 synthetic recipes were performed and characterized per duplicate, from which a subset of 307 recipes leading to the controlled formation of hollow NCs were further analyzed to correlate reaction conditions with the final obtained structure and stability (reproducibility). As a result, we present robust general synthetic protocols leading to the ad hoc production of Pt-based hollow NCs with independent control of shell thickness, void size, surface roughness, and degree of porosity. © 2019 The Authors

  • Writing chemical patterns using electrospun fibers as nanoscale inkpots for directed assembly of colloidal nanocrystals

    Kiremitler N.B., Torun I., Altintas Y., Patarroyo J., Demir H.V., Puntes V.F., Mutlugun E., Onses M.S. Nanoscale; 12 (2): 895 - 903. 2020. 10.1039/c9nr08056b. IF: 6.895

    Applications that range from electronics to biotechnology will greatly benefit from low-cost, scalable and multiplex fabrication of spatially defined arrays of colloidal inorganic nanocrystals. In this work, we present a novel additive patterning approach based on the use of electrospun nanofibers (NFs) as inkpots for end-functional polymers. The localized grafting of end-functional polymers from spatially defined nanofibers results in covalently bound chemical patterns. The main factors that determine the width of the nanopatterns are the diameter of the NF and the extent of spreading during the thermal annealing process. Lowering the surface energy of the substrates via silanization and a proper choice of the grafting conditions enable the fabrication of nanoscale patterns over centimeter length scales. The fabricated patterns of end-grafted polymers serve as the templates for spatially defined assembly of colloidal metal and metal oxide nanocrystals of varying sizes (15 to 100 nm), shapes (spherical, cube, rod), and compositions (Au, Ag, Pt, TiO2), as well as semiconductor quantum dots, including the assembly of semiconductor nanoplatelets. © 2019 The Royal Society of Chemistry.


  • Biodistribution, excretion, and toxicity of inorganic nanoparticles

    Casals E., Casals G., Puntes V., Rosenholm J.M. Theranostic Bionanomaterials; : 3 - 26. 2019. 10.1016/B978-0-12-815341-3.00001-8.

    The aim of this chapter is to provide a summary of the current knowledge of the full life cycle of inorganic nanoparticles (NPs) in physiological environments related to medical applications. The response of NPs inside organisms or released into the environment is complex and diverse, and a variety of parameters are involved: NPs may be aggregated into microscopic particles or embedded in exposed materials; their surfaces, which determine their bioactivity, experience constant modifications; NPs may corrode and dissolve; or they can suffer morphological modifications. Thus in physiological environments and inside the body, the effects, biodistribution, potential toxicity, and fate of NPs depend not only on their composition and designed morphological and surface properties, but mainly on the modifications they undergo depending on the exposure media. All this is reviewed and discussed in this chapter. © 2019 Elsevier Inc. All rights reserved.


  • Aging reduces the toxicity of pristine but not sulphidised silver nanoparticles to soil bacteria

    Schultz C.L., Gray J., Verweij R.A., Busquets-Fité M., Puntes V., Svendsen C., Lahive E., Matzke M. Environmental Science: Nano; 5 (11): 2618 - 2630. 2018. 10.1039/C8EN00054A. IF: 6.087

    In the environment engineered nanoparticles (ENPs) are subject to chemical and physical transformation processes. Thus, to understand their impact, it is important to consider how bioavailability and toxicity are influenced by these “aging” transformations with relation to environmental conditions and ENP properties. Here, two soil bacteria were exposed to Ag ENPs in ISO media (± fulvic acid) and soil pore water extracts with pH 6 and pH 8. The ENPs tested were 49 nm unfunctionalised, citrate stabilised (Ag-citr), 58 nm PVP-coated (Ag-PVP) and 36 nm sulphidised (Ag2S-PVP); AgNO3 was used as a positive control. Exposures were carried out using pristine (unaged) and 24 h aged ENPs, and the 24 h soluble fraction. Overall, toxicity was ranked AgNO3 > Ag-PVP ≥ Ag-citr ≫ Ag2S. Aging of AgNO3, Ag-PVP and Ag-citr in the ISO medium caused little change from unaged exposures and growth inhibition was mainly caused by soluble silver. Added fulvic acid decreased silver toxicity after aging and reduced the contribution of dissolution; as was the case in the soil pore waters where toxicity could not be attributed to ionic silver. Ag2S toxicity to A. globiformis in both ISO variants increased after aging, yet followed the same patterns as the metallic ENPs in the pore waters. For all ENPs pH effects were species dependent. Together this data showed that aging reduced toxicity in media with organic matter and despite soluble silver being the main driver of pristine ENP toxicity in the standard ISO medium, dissolution did not fully explain toxicity in the presence of organic matter. © The Royal Society of Chemistry.

  • Characterization of nanoparticle batch-to-batch variability

    Mülhopt S., Diabaté S., Dilger M., Adelhelm C., Anderlohr C., Bergfeldt T., de la Torre J.G., Jiang Y., Valsami-Jones E., Langevin D., Lynch I., Mahon E., Nelissen I., Piella J., Puntes V., Ray S., Schneider R., Wilkins T., Weiss C., Paur H.-R. Nanomaterials; 8 (5, 311) 2018. 10.3390/nano8050311. IF: 3.504

    A central challenge for the safe design of nanomaterials (NMs) is the inherent variability of NM properties, both as produced and as they interact with and evolve in, their surroundings. This has led to uncertainty in the literature regarding whether the biological and toxicological effects reported for NMs are related to specific NM properties themselves, or rather to the presence of impurities or physical effects such as agglomeration of particles. Thus, there is a strong need for systematic evaluation of the synthesis and processing parameters that lead to potential variability of different NM batches and the reproducible production of commonly utilized NMs. The work described here represents over three years of effort across 14 European laboratories to assess the reproducibility of nanoparticle properties produced by the same and modified synthesis routes for four of the OECD priority NMs (silica dioxide, zinc oxide, cerium dioxide and titanium dioxide) as well as amine-modified polystyrene NMs, which are frequently employed as positive controls for nanotoxicity studies. For 46 different batches of the selected NMs, all physicochemical descriptors as prioritized by the OECD have been fully characterized. The study represents the most complete assessment of NMs batch-to-batch variability performed to date and provides numerous important insights into the potential sources of variability of NMs and how these might be reduced. © 2018 by the authors. Licensee MDPI, Basel, Switzerland.

  • Fluorescently labelled nanomaterials in nanosafety research: Practical advice to avoid artefacts and trace unbound dye

    Murray R.A., Escobar A., Bastús N.G., Andreozzi P., Puntes V., Moya S.E. NanoImpact; 9: 102 - 113. 2018. 10.1016/j.impact.2017.11.001. IF: 0.000

    Fluorescence labelling has become a fundamental tool in nanotoxicological research. There are, however, certain drawbacks when dealing with the labelling of nanomaterials. Very often the leaching of dye from the nanomaterial or the presence of unbound dyes in solution leads to the incorrect quantification and localisation of nanomaterials in cells. In this review article we will discuss possible situations, which may give rise to incorrect quantification of the fluorescence associated with nanomaterials and their consequences in the evaluation of the fate of the nanomaterial and its intracellular dose. Issues related to the labelling strategies, dye photostability, impact of the dye on the properties of the nanomaterial surface, and the presence of unbound dye will be discussed. We will also show how Fluorescence Correlation Spectroscopy can be used to trace the presence of free label in solution. In addition, we will discuss the interaction of fluorescence molecules with metallic nanoparticles which can lead to an enhancement or quenching of fluorescence depending on the distance between the dye and the nanoparticle surface. Finally, we will compare the fluorescence emission originating from quantum dots and organic molecules. © 2017 Elsevier B.V.

  • Influence of soil porewater properties on the fate and toxicity of silver nanoparticles to Caenorhabditis elegans

    Schultz C.L., Lahive E., Lawlor A., Crossley A., Puntes V., Unrine J.M., Svendsen C., Spurgeon D.J. Environmental Toxicology and Chemistry; 37 (10): 2609 - 2618. 2018. 10.1002/etc.4220. IF: 3.179

    Engineered nanoparticles (NPs) entering the environment are subject to various transformations that in turn influence how particles are presented to, and taken up by, organisms. To understand the effect of soil properties on the toxicity of nanosilver to Caenorhabditis elegans, toxicity assays were performed in porewater extracts from natural soils with varying organic matter content and pH using 3–8 nm unfunctionalized silver (Ag 3–8Unf), 52-nm polyvinylpyrrolidone (PVP)-coated Ag NPs (Ag 52PVP), and AgNO 3 as ionic Ag. Effects on NP agglomeration and stability were investigated using ultraviolet-visible (UV-vis) spectroscopy and asymmetric flow field-flow fractionation (AF4); Ag + showed greater overall toxicity than nanosilver, with little difference between the NP types. Increasing soil organic matter content significantly decreased the toxicity of Ag 3–8Unf, whereas it increased that of AgNO 3 . The toxicity of all Ag treatments significantly decreased with increasing porewater pH. Dissolution of both NPs in the porewater extracts was too low to have contributed to their observed toxic effects. The UV-vis spectroscopy revealed low levels of agglomeration/aggregation independent of soil properties for Ag 3–8Unf, whereas higher organic matter as well as low pH appeared to stabilize Ag 52PVP. Overall, both soil organic matter content and pH affected NP fate as well as toxicity to C. elegans; however, there appears to be no clear connection between the measured particle characteristics and their effect. Environ Toxicol Chem 2018;37:2609–2618. © 2018 SETAC. © 2018 SETAC

  • Inter-laboratory comparison of nanoparticle size measurements using dynamic light scattering and differential centrifugal sedimentation

    Langevin D., Lozano O., Salvati A., Kestens V., Monopoli M., Raspaud E., Mariot S., Salonen A., Thomas S., Driessen M., Haase A., Nelissen I., Smisdom N., Pompa P.P., Maiorano G., Puntes V., Puchowicz D., Stępnik M., Suárez G., Riediker M., Benetti F., Mičetić I., Venturini M., Kreyling W.G., van der Zande M., Bouwmeester H., Milani S., Rädler J.O., Mülhopt S., Lynch I., Dawson K. NanoImpact; 10: 97 - 107. 2018. 10.1016/j.impact.2017.12.004. IF: 0.000

    Nanoparticle in vitro toxicity studies often report contradictory results with one main reason being insufficient material characterization. In particular the characterization of nanoparticles in biological media remains challenging. Our aim was to provide robust protocols for two of the most commonly applied techniques for particle sizing, i.e. dynamic light scattering (DLS) and differential centrifugal sedimentation (DCS) that should be readily applicable also for users not specialized in nanoparticle physico-chemical characterization. A large number of participants (40, although not all participated in all rounds) were recruited for a series of inter-laboratory comparison (ILC) studies covering many different instrument types, commercial and custom-built, as another possible source of variation. ILCs were organized in a consecutive manner starting with dispersions in water employing well-characterized near-spherical silica nanoparticles (nominal 19 nm and 100 nm diameter) and two types of functionalized spherical polystyrene nanoparticles (nominal 50 nm diameter). At first each laboratory used their in-house established procedures. In particular for the 19 nm silica particles, the reproducibility of the methods was unacceptably high (reported results were between 10 nm and 50 nm). When comparing the results of the first ILC round it was observed that the DCS methods performed significantly worse than the DLS methods, thus emphasizing the need for standard operating procedures (SOPs). SOPs have been developed by four expert laboratories but were tested for robustness by a larger number of independent users in a second ILC (11 for DLS and 4 for DCS). In a similar approach another SOP for complex biological fluids, i.e. cell culture medium containing serum was developed, again confirmed via an ILC with 8 participating laboratories. Our study confirms that well-established and fit-for-purpose SOPs are indispensable for obtaining reliable and comparable particle size data. Our results also show that these SOPs must be optimized with respect to the intended measurement system (e.g. particle size technique, type of dispersant) and that they must be sufficiently detailed (e.g. avoiding ambiguity regarding measurand definition, etc.). SOPs may be developed by a small number of expert laboratories but for their widespread applicability they need to be verified by a larger number of laboratories. © 2017 Elsevier B.V.

  • Low-Cost Strategy for the Development of a Rapid Electrochemical Assay for Bacteria Detection Based on AuAg Nanoshells

    Russo L., Leva Bueno J., Bergua J.F., Costantini M., Giannetto M., Puntes V., De La Escosura-Muñiz A., Merkoçi A. ACS Omega; 3 (12): 18849 - 18856. 2018. 10.1021/acsomega.8b02458.

    A low-cost strategy for the simple and rapid detection of bacterial cells in biological matrixes is presented herein. Escherichia coli and Salmonella typhimurium were chosen as model bacteria for the development of an electrochemical assay based on hollow AuAg nanoshells (NSs). By taking advantage of their electrocatalytic properties for the in situ generation of the electrochemical signal without the need of any other kind of reagent, substrate, or redox enzyme, high sensitivities (down to 102 CFU/mL) were achieved. Moreover, the recognition and discrimination of the model bacterial cells in the sample matrix was possible by relying solely on nonspecific affinity interactions between their cell walls and AuAg NSs surface, avoiding the use of expensive and fragile biological receptor. Compared to traditional, laboratory-based analytical tests available, this assay provides a promising proof-of-concept alternative that allows to obtain good sensitivities and selectivity in very short times in addition to the low cost. © 2018 American Chemical Society.

  • Plasmonic assemblies of gold nanorods on nanoscale patterns of poly(ethylene glycol): Application in surface-enhanced Raman spectroscopy

    Karabel Ocal S., Patarroyo J., Kiremitler N.B., Pekdemir S., Puntes V.F., Onses M.S. Journal of Colloid and Interface Science; 532: 449 - 455. 2018. 10.1016/j.jcis.2018.07.124. IF: 5.091

    Approaches are needed for the tailored assembly of plasmonic building blocks on the surface of substrates to synergistically enhance their properties. Here we demonstrate selective immobilization and assembly of gold nanorods (NRs) on substrates modified and patterned with end-grafted poly(ethylene glycol) (PEG) layers. The ligand exchange from the initial cetyltrimethylammonium bromide to sodium citrate was necessary for the immobilization of gold NRs onto PEG grafted substrates. Linear nanopatterns of PEG were fabricated using electrospun nanofibers as masks in oxygen plasma etching. The selective immobilization of citrate-stabilized gold NRs with a length of ∼50 nm and a width of 20 nm on the nanopatterned PEG layers led to linear and registered arrays of rods. The number of gold NRs per line depended on the width of the patterns and approached 1 when the width of the patterns was comparable to the length of the rods. The confinement of the binding regions led to a ∼3 fold increase in the number of gold NRs immobilized per unit area. The selective and dense immobilization of gold NRs on the nanoscale patterns of PEG resulted in spatially defined and strong surface-enhanced Raman scattering activity enabling detection of molecules at concentrations as low as 1 nM. © 2018

  • Sequential Deconstruction-Reconstruction of Metal-Organic Frameworks: An Alternative Strategy for Synthesizing (Multi)-Layered ZIF Composites

    Avci C., Yazdi A., Tarrés M., Bernoud E., Bastús N.G., Puntes V., Imaz I., Ribas X., Maspoch D. ACS Applied Materials and Interfaces; 10 (28): 23952 - 23960. 2018. 10.1021/acsami.8b05098. IF: 8.097

    Here, we report the synthesis of (multi)-layered zeolitic imidazolate framework (ZIF-8/-67) composite particles via a sequential deconstruction-reconstruction process. We show that this process can be applied to construct ZIF-8-on-ZIF-67 composite particles whose cores are the initially etched particles. In addition, we demonstrate that introduction of functional inorganic nanoparticles (INPs) onto the crystal surface of etched particles does not disrupt ZIF particle reconstruction, opening new avenues for designing (multi)-layered ZIF-on-INP-on-ZIF composite particles comprising more than one class of inorganic nanoparticles. In these latter composites, the location of the inorganic nanoparticles inside each single metal-organic framework particle as well as of their separation at the nanoscale (20 nm) is controlled. Preliminary results show that (multi)-layered ZIF-on-INP-on-ZIF composite particles comprising a good sequence of inorganic nanoparticles can potentially catalyze cascade reactions. Copyright © 2018 American Chemical Society.

  • Time- and Size-Resolved Plasmonic Evolution with nm Resolution of Galvanic Replacement Reaction in AuAg Nanoshells Synthesis

    Russo L., Merkoçi F., Patarroyo J., Piella J., Merkoçi A., Bastús N.G., Puntes V. Chemistry of Materials; 30 (15): 5098 - 5107. 2018. 10.1021/acs.chemmater.8b01488. IF: 9.890

    The rational design of advanced nanomaterials with enhanced optical properties can be reached only with the profound thermodynamic and kinetic understanding of their synthetic processes. In this work, the synthesis of monodisperse AuAg nanoshells with thin shells and large voids is achieved through the development of a highly reproducible and robust methodology based on the galvanic replacement reaction. This is obtained thanks to the systematic identification of the role played by the different synthetic parameters involved in the process (such as surfactants, co-oxidizers, complexing agents, time, and temperature), providing an unprecedented control over the material's morphological and optical properties. Thus, the time- and size-resolved evolution of AuAg nanoshells surface plasmon resonance band is described for 15, 30, 60, 80, 100, and 150 nm-sized particles spanning almost through the entire visible spectrum. Its analysis reveals a four-phase mechanism coherent with the material's morphological transformation. Simulations based on Mie's theory confirm the observed optical behavior in AuAg nanoshells formation and provide insights into the influence of the Au/Ag ratio on their plasmonic properties. The high degree of morphological control provided by this methodology represents a transferable and scalable strategy for the development of advanced-generation plasmonic nanomaterials. © 2018 American Chemical Society.

  • Tunable electrochemistry of gold-silver alloy nanoshells

    Russo L., Puntes V., Merkoçi A. Nano Research; 11 (12): 6336 - 6345. 2018. 10.1007/s12274-018-2157-y. IF: 7.994

    The widespread and increasing interest in enhancing biosensing technologies by increasing their sensitivities and lowering their costs has led to the exploration and application of complex nanomaterials as signal transducers and enhancers. In this work, the electrochemical properties of monodispersed AuAg alloy nanoshells (NSs) with finely tunable morphology, composition, and size are studied to assess their potential as electroactive labels. The controlled corrosion of their silver content, caused by the oxidizing character of dissolved oxygen and chlorides of the electrolyte, allows the generation of a reproducible electrochemical signal that is easily measurable through voltammetric techniques. Remarkably, the underpotential deposition of dissolved Ag+ catalyzed on AuAg NS surfaces is observed and its dependence on the nanoparticle morphology, size, and elemental composition is studied, revealing a strong correlation between the relative amounts of the two metals. The highest catalytic activity is found at Au/Ag ratios higher than ≈ 10, showing how the synergy between both metals is necessary to trigger the enhancement of Ag+ reduction. The ability of AuAg NSs to generate an electrocatalytic current without the need for any strong acid makes them an extremely promising material for biosensing applications. [Figure not available: see fulltext.]. © 2018, Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature.


  • Assembly of Plasmonic Nanoparticles on Nanopatterns of Polymer Brushes Fabricated by Electrospin Nanolithography

    Kiremitler N.B., Pekdemir S., Patarroyo J., Karabel S., Torun I., Puntes V.F., Onses M.S. ACS Macro Letters; 6 (6): 603 - 608. 2017. 10.1021/acsmacrolett.7b00288. IF: 6.185

    This paper presents electrospin nanolithography (ESPNL) for versatile and low-cost fabrication of nanoscale patterns of polymer brushes to serve as templates for assembly of metallic nanoparticles. Here electrospun nanofibers placed on top of a substrate grafted with polymer brushes serve as masks. The oxygen plasma etching of the substrate followed by removal of the fibers leads to linear patterns of polymer brushes. The line-widths as small as ∼50 nm can be achieved by precise tuning of the diameter of fibers, etching condition, and fiber-substrate interaction. Highly aligned and spatially defined patterns can be fabricated by operating in the near-field electrospinning regime. Patterns of polymer brushes with two different chemistries effectively directed the assembly of gold nanoparticles and silver nanocubes. Nanopatterned brushes imparted strong confinement effects on the assembly of plasmonic nanoparticles and resulted in strong localization of electromagnetic fields leading to intense signals in surface-enhanced Raman spectroscopy. The scalability and simplicity of ESPNL hold great promise in patterning of a broad range of polymer thin films for different applications. © 2017 American Chemical Society.

  • Bacterial endotoxin (lipopolysaccharide) binds to the surface of gold nanoparticles, interferes with biocorona formation and induces human monocyte inflammatory activation

    Li Y., Shi Z., Radauer-Preiml I., Andosch A., Casals E., Luetz-Meindl U., Cobaleda M., Lin Z., Jaberi-Douraki M., Italiani P., Horejs-Hoeck J., Himly M., Monteiro-Riviere N.A., Duschl A., Puntes V.F., Boraschi D. Nanotoxicology; 11 (9-10): 1157 - 1175. 2017. 10.1080/17435390.2017.1401142. IF: 6.428

    Nanoparticles (NPs) are easily contaminated by bacterial endotoxin (lipopolysaccharide [LPS]). The presence of LPS can be responsible for many immune/inflammatory effects attributed to NPs. In this study, we examined the effects of LPS adsorption on the NP surface on the formation of a biocorona in biological fluids and on the subsequent inflammation-inducing activity of NPs. Different gold (Au) NPs with sizes ranging from 10 to 80 nm and with different surface functionalization (sodium citrate, lipoic acid, and branched polyethyleneimine (BPEI), or polyethylene glycol (PEG)) were exposed to E. coli LPS under different conditions. The binding capacity of LPS to the surface of AuNPs was dose- and time-dependent. LPS attached to sodium citrate and lipoic acid coatings, but did not adhere to BPEI- or PEG-coated NPs. By computational simulation, the binding of LPS to AuNPs seems to follow the Langmuir absorption isotherm. The presence of LPS on AuNP surface interfered and caused a decrease in the formation of the expected biomolecular corona upon incubation in human plasma. LPS-coated AuNPs, but not the LPS-free NPs, induced significant inflammatory responses in vitro. Notably, while free LPS did also induce an anti-inflammatory response, LPS bound to NPs appeared unable to do so. In conclusion, the unintentional adsorption of LPS onto the NP surface can affect the biocorona formation and the inflammatory properties of NPs. Thus, for an accurate interpretation of NP interactions with cells, it is extremely important to be able to distinguish the intrinsic NP biological effects from those caused by biologically active contaminants such as endotoxin. © 2017 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

  • Cancer resistance to treatment and antiresistance tools offered by multimodal multifunctional nanoparticles

    Casals E., Gusta M.F., Cobaleda-Siles M., Garcia-Sanz A., Puntes V.F. Cancer Nanotechnology; 8 (1, 7) 2017. 10.1186/s12645-017-0030-4.

    Chemotherapeutic agents have limited efficacy and resistance to them limits today and will limit tomorrow our capabilities of cure. Resistance to treatment with anticancer drugs results from a variety of factors including individual variations in patients and somatic cell genetic differences in tumours. In front of this, multimodality has appeared as a promising strategy to overcome resistance. In this context, the use of nanoparticle-based platforms enables many possibilities to address cancer resistance mechanisms. Nanoparticles can act as carriers and substrates for different ligands and biologically active molecules, antennas for imaging, thermal and radiotherapy and, at the same time, they can be effectors by themselves. This enables their use in multimodal therapies to overcome the wall of resistance where conventional medicine crash as ageing of the population advance. In this work, we review the cancer resistance mechanisms and the advantages of inorganic nanomaterials to enable multimodality against them. In addition, we comment on the need of a profound understanding of what happens to the nanoparticle-based platforms in the biological environment for those possibilities to become a reality. © 2017, The Author(s).

  • Confining Functional Nanoparticles into Colloidal Imine-Based COF Spheres by a Sequential Encapsulation–Crystallization Method

    Rodríguez-San-Miguel D., Yazdi A., Guillerm V., Pérez-Carvajal J., Puntes V., Maspoch D., Zamora F. Chemistry - A European Journal; 23 (36): 8623 - 8627. 2017. 10.1002/chem.201702072. IF: 5.317

    Here, a two-step method is reported that enables imparting new functionalities to covalent organic frameworks (COFs) by nanoparticle confinement. The direct reaction between 1,3,5-tris(4-aminophenyl)benzene and 1,3,5-benzenetricarbaldehyde in the presence of a variety of metallic/metal-oxide nanoparticles resulted in embedding of the nanoparticles in amorphous and non-porous imine-linked polymer organic spheres (NP@a-1). Post-treatment reactions of NP@a-1 with acetic acid under reflux led to crystalline and porous imine-based COF-hybrid spheres (NP@c-1). Interestingly, Au@c-1 and Pd@c-1 were found to be catalytically active. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

  • Conserved effects and altered trafficking of Cetuximab antibodies conjugated to gold nanoparticles with precise control of their number and orientation

    García-Fernández L., Garcia-Pardo J., Tort O., Prior I., Brust M., Casals E., Lorenzo J., Puntes V.F. Nanoscale; 9 (18): 6111 - 6121. 2017. 10.1039/c7nr00947j. IF: 7.367

    Gold nanoparticles (17 nm) have been functionalized with the antiangiogenic monoclonal antibody drug Cetuximab at a well-defined orientation and coverage density of antibodies. Functionalization has been carried out through site-directed chemistry via the selective oxidation of the carbohydrate moiety of antibodies linked to a thiolated hydrazide. A431 tumor cells have been exposed to these conjugates for in vitro evaluation of their effects. In addition to epithelial growth factor receptor blocking, trafficking and signaling alterations were also observed. Thus, the blocking effects of Cetuximab were increased and sustained for a longer time when associated with the nanoparticles. Enhancing antibody therapy effects by decreasing the needed dose and prolonging its effect by avoiding receptor recycling may serve to obtain increased therapeutic benefits for immunotherapy. © The Royal Society of Chemistry 2017.

  • Core-shell Au/CeO2 nanoparticles supported in UiO-66 beads exhibiting full CO conversion at 100 °c

    Yazdi A., Abo Markeb A., Garzón-Tovar L., Patarroyo J., Moral-Vico J., Alonso A., Sánchez A., Bastus N., Imaz I., Font X., Puntes V., Maspoch D. Journal of Materials Chemistry A; 5 (27): 13966 - 13970. 2017. 10.1039/c7ta03006a. IF: 8.867

    Hybrid core-shell Au/CeO2 nanoparticles (NPs) dispersed in UiO-66 shaped into microspherical beads are created using the spray-drying continuous-flow method. The combined catalytic properties of nanocrystalline CeO2 and Au in a single particle and the support and protective function of porous UiO-66 beads make the resulting composites show good performances as catalysts for CO oxidation (T50 = 72 °C; T100 = 100 °C) and recyclability. © 2017 The Royal Society of Chemistry.

  • Corrigendum: Intrinsic and extrinsic properties affecting innate immune responses to nanoparticles: The case of cerium oxide [Front Immunol, 8, (2017) (970)] doi: 10.3389/fimmu.2017.00970

    Casals E., Gusta M.F., Piella J., Casals G., Jiménez W., Puntes V. Frontiers in Immunology; 8 (DEC, 1891) 2017. 10.3389/fimmu.2017.01891.

    In the original article, we overlooked to include the FutureNanoNeeds Project financed by the European Community under the FP7 Programme under Grant Agreement No. 604602 (FP7-NMP-2013-LARGE-7, Grant Agreement No. 604602) to Victor Puntes. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. A correction has been made to the text in the Funding: "Financial support from the FutureNanoNeeds Project (GA: 604602) financed by the European Community under the FP7 Programme (FP7-NMP-2013-LARGE-7) is gratefully acknowledged." The original article was updated. © 2017 Casals, Gusta, Piella, Casals, Jiménez and Puntes.

  • Critical review of existing nanomaterial adsorbents to capture carbon dioxide and methane

    Alonso A., Moral-Vico J., Abo Markeb A., Busquets-Fité M., Komilis D., Puntes V., Sánchez A., Font X. Science of the Total Environment; 595: 51 - 62. 2017. 10.1016/j.scitotenv.2017.03.229. IF: 4.900

    Innovative gas capture technologies with the objective to mitigate CO2 and CH4 emissions are discussed in this review. Emphasis is given on the use of nanoparticles (NP) as sorbents of CO2 and CH4, which are the two most important global warming gases. The existing NP sorption processes must overcome certain challenges before their implementation to the industrial scale. These are: i) the utilization of the concentrated gas stream generated by the capture and gas purification technologies, ii) the reduction of the effects of impurities on the operating system, iii) the scale up of the relevant materials, and iv) the retrofitting of technologies in existing facilities. Thus, an innovative design of adsorbents could possibly address those issues. Biogas purification and CH4 storage would become a new motivation for the development of new sorbent materials, such as nanomaterials. This review discusses the current state of the art on the use of novel nanomaterials as adsorbents for CO2 and CH4. The review shows that materials based on porous supports that are modified with amine or metals are currently providing the most promising results. The Fe3O4-graphene and the MOF-117 based NPs show the greatest CO2 sorption capacities, due to their high thermal stability and high porosity. Conclusively, one of the main challenges would be to decrease the cost of capture and to scale-up the technologies to minimize large-scale power plant CO2 emissions. © 2017 Elsevier B.V.

  • Domain Formation and Conformational Changes in Gold Nanoparticle Conjugates Studied Using DPD Simulations

    Raman A., Jaime C., Puntes V.F. Langmuir; 33 (50): 14502 - 14512. 2017. 10.1021/acs.langmuir.7b03318. IF: 3.833

    A gold nanoparticle (AuNP) conjugate formed with 11-mercaptoundecanoic acid (MUA) and thiolated polyethylene glycol (SH-PEG) is simulated using dissipative particle dynamics (DPD) methods, obtaining an excellent agreement with previous experimental observations. The simulations cover the isolated components (AuNP, MUA, and SH-PEG), as well as pairs of components, and finally the all three components at the same time. In this latter case, changes in the order of addition of MUA and SH-PEG over the AuNP are also considered. The AuNP is formed by independent gold beads and keeps an almost spherical shape throughout the simulation. MUA forms micelles of four to six MUA units when dispersed in water, while SH-PEG stays individually and well solvated. When exposed to AuNP, both molecules show a tendency to form patches on the surface. SH-PEG displays two different conformations (radial and tangential) depending on its relative concentration and the presence of other molecules at the NP surface. When combined at subsaturation concentrations, MUA arrives faster to the AuNP surface than SH-PEG and forms patches while SH-PEG occupies the remaining free surface. In these conditions, the order of addition of the different components partially alters these results. When SH-PEG is added over an already formed MUA/AuNP partial layer, it adopts a radial conformation over the MUA formed patches; on the contrary, if MUA is added over an already formed SH-PEG/AuNP partial layer, much less SH-PEGs adopt a radial conformation and MUA patches are significantly smaller. © 2017 American Chemical Society.

  • Formation of the Protein Corona: The Interface between Nanoparticles and the Immune System

    Barbero F., Russo L., Vitali M., Piella J., Salvo I., Borrajo M.L., Busquets-Fité M., Grandori R., Bastús N.G., Casals E., Puntes V. Seminars in Immunology; 34: 52 - 60. 2017. 10.1016/j.smim.2017.10.001. IF: 9.611

    The interaction of inorganic nanoparticles and many biological fluids often withstands the formation of a Protein Corona enveloping the nanoparticle. This Protein Corona provides the biological identity to the nanoparticle that the immune system will detect. The formation of this Protein Corona depends not only on the composition of the nanoparticle, its size, shape, surface state and exposure time, but also on the type of media, nanoparticle to protein ratio and the presence of ions and other molecular species that interfere in the interaction between proteins and nanoparticles. This has important implications on immune safety, biocompatibility and the use of nanoparticles in medicine. © 2017 Elsevier Ltd

  • Hollow metal nanostructures for enhanced plasmonics: Synthesis, local plasmonic properties and applications

    Genç A., Patarroyo J., Sancho-Parramon J., Bastús N.G., Puntes V., Arbiol J. Nanophotonics; 6 (1): 193 - 213. 2017. 10.1515/nanoph-2016-0124. IF: 4.492

    Metallic nanostructures have received great attention due to their ability to generate surface plasmon resonances, which are collective oscillations of conduction electrons of a material excited by an electromagnetic wave. Plasmonic metal nanostructures are able to localize and manipulate the light at the nanoscale and, therefore, are attractive building blocks for various emerging applications. In particular, hollow nanostructures are promising plasmonic materials as cavities are known to have better plasmonic properties than their solid counterparts thanks to the plasmon hybridization mechanism. The hybridization of the plasmons results in the enhancement of the plasmon fields along with more homogeneous distribution as well as the reduction of localized surface plasmon resonance (LSPR) quenching due to absorption. In this review, we summarize the efforts on the synthesis of hollow metal nanostructures with an emphasis on the galvanic replacement reaction. In the second part of this review, we discuss the advancements on the characterization of plasmonic properties of hollow nanostructures, covering the single nanoparticle experiments, nanoscale characterization via electron energy-loss spectroscopy and modeling and simulation studies. Examples of the applications, i.e. sensing, surface enhanced Raman spectroscopy, photothermal ablation therapy of cancer, drug delivery or catalysis among others, where hollow nanostructures perform better than their solid counterparts, are also evaluated. © 2016 Aziz Genç, Jordi Arbiol et al., published by De Gruyter.

  • Intrinsic and extrinsic properties affecting innate immune responses to nanoparticles: The case of cerium oxide

    Casals E., Gusta M.F., Piella J., Casals G., Jiménez W., Puntes V. Frontiers in Immunology; 8 (AUG, 970) 2017. 10.3389/fimmu.2017.00970. IF: 6.429

    We review the apparent discrepancies between studies that report anti-inflammatory effects of cerium oxide nanoparticles (CeO2 NPs) through their reactive oxygen specieschelating properties and immunological studies highlighting their toxicity. We observe that several underappreciated parameters, such as aggregation size and degree of impurity, are critical determinants that need to be carefully addressed to better understand the NP biological effects in order to unleash their potential clinical benefits. This is because NPs can evolve toward different states, depending on the environment where they have been dispersed and how they have been dispersed. As a consequence, final characteristics of NPs can be very different from what was initially designed and produced in the laboratory. Thus, aggregation, corrosion, and interaction with extracellular matrix proteins critically modify NP features and fate. These modifications depend to a large extent on the characteristics of the biological media in which the NPs are dispersed. As a consequence, when reviewing the scientific literature, it seems that the aggregation state of NPs, which depends on the characteristics of the dispersing media, may be more significant than the composition or original size of the NPs. In this work, we focus on CeO2 NPs, which are reported sometimes to be protective and anti-inflammatory, and sometimes toxic and pro-inflammatory. © 2017 Casals, Gusta, Piella, Casals, Jiménez and Puntes.

  • Modeling the Optical Responses of Noble Metal Nanoparticles Subjected to Physicochemical Transformations in Physiological Environments: Aggregation, Dissolution and Oxidation

    Piella J., Bastús N.G., Puntes V. Zeitschrift fur Physikalische Chemie; 231 (1): 33 - 50. 2017. 10.1515/zpch-2016-0874. IF: 1.012

    Herein, we study how optical properties of colloidal dispersions of noble metal nanoparticles (Au and Ag) are affected by processes such as aggregation and oxidative dissolution. The optical contributions of these processes to the extinction spectra in the UV-vis region are often overlapped, making difficult its interpretation. In this regard, modeling the UV-vis spectra (in particular absorbance curve, peaks position, intensity and full width at half maximum-FWHM) of each process separately offers a powerful tool to identify the transformation of NPs under relevant and complex scenarios, such as in biological media. The proper identification of these transformations is crucial to understand the biological effects of the NPs. © 2017 Walter de Gruyter GmbH, Berlin/Boston.

  • One-Pot Synthesis of Cationic Gold Nanoparticles by Differential Reduction

    Sperling R.A., Garciá-Fernández L., Ojea-Jiménez I., Piella J., Bastús N.G., Puntes V. Zeitschrift fur Physikalische Chemie; 231 (1): 7 - 18. 2017. 10.1515/zpch-2016-0864. IF: 1.012

    The size-controlled synthesis of cationic particles by differential reduction of HAuCl4 precursor in the presence of NaBH4 and 1-aminoundecane-12-thiol (AUT) is reported. The number of seed particles is determined by the fraction of the initially Au precursor reduced by NaBH4 present in the reaction mixture, which are then grown larger by the AUT, acting as both weak reducing agent and stabilizing surfactant. By this methodology, size controlled synthesis is achieved in a two-step one-pot synthesis at room temperature. © 2017 Walter de Gruyter GmbH, Berlin/Boston.

  • Probing the surface reactivity of nanocrystals by the catalytic degradation of organic dyes: The effect of size, surface chemistry and composition

    Piella J., Merkoçi F., Genç A., Arbiol J., Bastús N.G., Puntes V. Journal of Materials Chemistry A; 5 (23): 11917 - 11929. 2017. 10.1039/c7ta01328k. IF: 8.867

    We herein present a comprehensive study on how the catalytic performance and reusability of Au nanocrystals (NCs) are affected by systematic variations of crystal size, surface coating and composition. The reductions of different organic dyes (4-nitrophenol, rhodamine B and methylene blue) by borohydride ions were used as model catalytic reactions. The catalytic performance of the Au NCs ranged between 3.6 to 110 nm was found to be dependent on crystal size, indicating that Au surface atoms have a distinct size-dependent reactivity in this reaction. Similarly, the catalytic performance was found to be strongly dependent on the nature of the coating molecule, obtaining lower catalytic activities for molecules strongly bound to the Au surface. Finally, the catalytic performance was found to be dependent on the chemical composition of the NC (Au, Ag, Pt) and the model dye used as a testing system, with the highest degradation rate found for methylene blue, followed by 4-nitrophenol and rhodamine B. We believe that this study provides a better understanding of the catalytic performance of Au NCs upon controlled modifications of the structural and morphological parameters, and a working environment that can be used to facilitate the selection of the optimum NC size, coating molecule and evaluation system for a particular study of interest. © 2017 The Royal Society of Chemistry.

  • Safer by design strategies

    Cobaleda-Siles M., Guillamon A.P., Delpivo C., Vázquez-Campos S., Puntes V.F. Journal of Physics: Conference Series; 838 (1, 012016) 2017. 10.1088/1742-6596/838/1/012016. IF: 0.000

    Throughout the EU funded FP7 project GUIDENano, we are trying to control and monitor the evolution of nano-enable products during their lifecycle. Small alterations of the nanoparticle (NP) state may have critical consequences on the NP behaviour and performance. For this reason it is important to highlight the importance of an extensive and proper characterization to define the NP physico-chemical characteristics under several environmental conditions. Furthermore, this characterization is necessary to ensure that obtained results are reproducible and allow understanding the behaviour of the NP on biological systems. In this paper different strategies reported in the literature regarding the safety-by-design concept are summarized. Several strategies from the synthetic point of view that help us to modulate the main factors which determine the safety of nanomaterials are proposed. © Published under licence by IOP Publishing Ltd.

  • Seeded Growth Synthesis of Au-Fe3O4 Heterostructured Nanocrystals: Rational Design and Mechanistic Insights

    Fantechi E., Roca A.G., Sepúlveda B., Torruella P., Estradé S., Peiró F., Coy E., Jurga S., Bastús N.G., Nogués J., Puntes V. Chemistry of Materials; 29 (9): 4022 - 4035. 2017. 10.1021/acs.chemmater.7b00608. IF: 9.466

    Multifunctional hybrid nanoparticles comprising two or more entities with different functional properties are gaining ample significance in industry and research. Due to its combination of properties, a particularly appealing example is Au-Fe3O4 composite nanoparticles. Here we present an in-depth study of the synthesis of Au-Fe3O4 heterostructured nanocrystals (HNCs) by thermal decomposition of iron precursors in the presence of preformed 10 nm Au seeds. The role of diverse reaction parameters on the HNCs formation was investigated using two different precursors: iron pentacarbonyl (Fe(CO)5) and iron acetylacetonate (Fe(acac)3). The reaction conditions promoting the heterogeneous nucleation of Fe3O4 onto Au seeds were found to significantly differ depending on the precursor chosen, where Fe(acac)3 is considerably more sensitive to the variation of the parameters than Fe(CO)5 and more subject to homogeneous nucleation processes with the consequent formation of isolated iron oxide nanocrystals (NCs). The role of the surfactants was also crucial in the formation of well-defined and monodisperse HNCs by regulating the access to the Au surface. Similarly, the variations of the [Fe]/[Au] ratio, temperature, and employed solvent were found to act on the mean size and the morphology of the obtained products. Importantly, while the optical properties are rather sensitive to the final morphology, the magnetic ones are rather similar for the different types of obtained HNCs. The surface functionalization of dimer-like HNCs with silica allows their dispersion in aqueous media, opening the path to their use in biomedical applications. © 2017 American Chemical Society.

  • Size-Dependent Protein-Nanoparticle Interactions in Citrate-Stabilized Gold Nanoparticles: The Emergence of the Protein Corona

    Piella J., Bastús N.G., Puntes V. Bioconjugate chemistry; 28 (1): 88 - 97. 2017. 10.1021/acs.bioconjchem.6b00575. IF: 4.818

    Surface modifications of highly monodisperse citrate-stabilized gold nanoparticles (AuNPs) with sizes ranging from 3.5 to 150 nm after their exposure to cell culture media supplemented with fetal bovine serum were studied and characterized by the combined use of UV-vis spectroscopy, dynamic light scattering, and zeta potential measurements. In all the tested AuNPs, a dynamic process of protein adsorption was observed, evolving toward the formation of an irreversible hard protein coating known as Protein Corona. Interestingly, the thickness and density of this protein coating were strongly dependent on the particle size, making it possible to identify different transition regimes as the size of the particles increased: (i) NP-protein complexes (or incomplete corona), (ii) the formation of a near-single dense protein corona layer, and (iii) the formation of a multilayer corona. In addition, the different temporal patterns in the evolution of the protein coating came about more quickly for small particles than for the larger ones, further revealing the significant role that size plays in the kinetics of this process. Since the biological identity of the NPs is ultimately determined by the protein corona and different NP-biological interactions take place at different time scales, these results are relevant to biological and toxicological studies.


  • Assessing the Immunosafety of Engineered Nanoparticles with a Novel in Vitro Model Based on Human Primary Monocytes

    Li Y., Italiani P., Casals E., Valkenborg D., Mertens I., Baggerman G., Nelissen I., Puntes V.F., Boraschi D. ACS Applied Materials and Interfaces; 8 (42): 28437 - 28447. 2016. 10.1021/acsami.6b06278. IF: 7.145

    The possibility that nanomaterials could perturb the normal course of an inflammatory response is a key issue when assessing nanoimmunosafety. The alteration of the normal progress of an inflammatory response may have pathological consequences, since inflammation is a major defensive mechanism and its efficiency maintains the body's health. The immunosafety of engineered nanoparticles at nontoxic concentrations was investigated with the use of a human primary monocyte-based in vitro system, which reproduces in a simplified fashion the full course of the physiological inflammatory response, from initiation and development to resolution. The kinetics of expression and production of inflammatory and anti-inflammatory cytokines and the proteomic profiles were used for describing the inflammatory defensive response. We assessed the ability of gold and silver nanoparticles to trigger inflammation and to interfere with the course of an ongoing defensive reaction. While neither nanoparticle type was able to directly activate monocytes, silver nanoparticles could exacerbate the inflammatory response of monocytes but did not interfere with the resolution of the inflammatory reaction. These findings support the use of human primary monocyte-based in vitro assays for realistically investigating the effects of engineered nanoparticles on human innate immune responses, in order to predict the immunological risk of nanomaterials and implement safe nanoparticle-based applications. © 2016 American Chemical Society.

  • Cerium oxide nanoparticles reduce steatosis, portal hypertension and display anti-inflammatory properties in rats with liver fibrosis

    Oró D., Yudina T., Fernández-Varo G., Casals E., Reichenbach V., Casals G., De La Presa B.G., Sandalinas S., Carvajal S., Puntes V., Jiménez W. Journal of Hepatology; 64 (3): 691 - 698. 2016. 10.1016/j.jhep.2015.10.020. IF: 10.590

    Background & Aims Cerium oxide nanoparticles (CeO2NPs) have proven to behave as free radical scavengers and/or anti-inflammatory agents. The aim of the study was to determine whether CeO2NPs display hepatoprotective properties in experimental chronic liver disease. Methods Systemic and hepatic effects of nanoparticles were assessed in CCl4-treated rats receiving CeO2NPs or vehicle twice weekly for two weeks and CCl4 treatment was continued for 8 additional weeks. Thereafter, mean arterial pressure and portal pressure (PP) were assessed and serum samples obtained to measure standard hepatic and renal function tests. Organ and subcellular distribution of NPs were assessed using mass spectrometry (ICP-MS) and transmission electron microscopy. Liver samples were obtained to evaluate steatosis, α-SMA expression, macrophage infiltration, apoptosis and mRNA expression of oxidative stress, inflammatory or vasoactive related genes. Results Most CeO2NPs were located in the liver and it reduced hepatic steatosis, ameliorated systemic inflammatory biomarkers and improved PP without affecting mean arterial pressure. In addition, a marked reduction in mRNA expression of inflammatory cytokines (TNFα, IL1β, COX-2, iNOS), ET-1 and messengers related to oxidative (Epx, Ncf1, Ncf2) or endoplasmic reticulum (Atf3, Hspa5) stress signaling pathways was observed in the liver of rats receiving CeO2NPs. This was associated with reduced macrophage infiltration and reduced abundance of caspase-3, α-SMA and inflammatory cytokines. Conclusions CeO2NPs administration to CCl4-treated rats protects against chronic liver injury by reducing liver steatosis and portal hypertension and markedly attenuating the intensity of the inflammatory response, thereby suggesting that CeO2NPs may be of therapeutic value in chronic liver disease. © 2015 European Association for the Study of the Liver.

  • Design and pharmacokinetical aspects for the use of inorganic nanoparticles in radiomedicine

    Puntes V. British Journal of Radiology; 89 (1057, 20150210) 2016. 10.1259/bjr.20150210. IF: 2.026

    The potential use of nanoparticles (NPs) in medicine is determined by the pharmacokinetical and biodistribution aspects that govern NP behaviour. In this context, diagnosis (low irradiation dose) and therapy (high irradiation dose) is about the same for the NP, as much as to deliver toxic doses of radiation or toxic doses of a chemotherapeutic agent. The NP effects also have to be correlated with how they interact, evolve and are transformed during their exposure to the human body, during their administration, distribution, metabolization and expulsion. Indeed, owing to interactions between NPs and components from the biological medium, NPs are known to suffer different types of alterations, such as loss of colloidal stability (aggregation and sedimentation), protein adsorption (and consequent exposure to or escape from the immune system) and chemical transformation (oxidation, corrosion and dissolution). Their original performance and these alterations have a major impact on NP behaviour and have to be taken into account for any intended use of them in medicine, also including their use for enhanced radiodiagnosis, radiotherapy and radiochemotherapy. © 2015 The Authors. Published by the British Institute of Radiology.

  • Enhanced detection with spectral imaging fluorescence microscopy reveals tissue- and cell-type-specific compartmentalization of surface-modified polystyrene nanoparticles

    Kenesei K., Murali K., Czéh Á., Piella J., Puntes V., Madarász E. Journal of Nanobiotechnology; 14 (1, 55) 2016. 10.1186/s12951-016-0210-0. IF: 4.239

    Background: Precisely targeted nanoparticle delivery is critically important for therapeutic applications. However, our knowledge on how the distinct physical and chemical properties of nanoparticles determine tissue penetration through physiological barriers, accumulation in specific cells and tissues, and clearance from selected organs has remained rather limited. In the recent study, spectral imaging fluorescence microscopy was exploited for precise and rapid monitoring of tissue- and cell-type-specific distribution of fluorescent polystyrene nanoparticles with chemically distinct surface compositions. Methods: Fluorescent polystyrene nanoparticles with 50-90 nm diameter and with carboxylated- or polyethylene glycol-modified (PEGylated) surfaces were delivered into adult male and pregnant female mice with a single intravenous injection. The precise anatomical distribution of the particles was investigated by confocal microscopy after a short-term (5 min) or long-term (4 days) distribution period. In order to distinguish particle-fluorescence from tissue autofluorescence and to enhance the detection-efficiency, fluorescence spectral detection was applied during image acquisition and a post hoc full spectrum analysis was performed on the final images. Results: Spectral imaging fluorescence microscopy allowed distinguishing particle-fluorescence from tissue-fluorescence in all examined organs (brain, kidney, liver, spleen and placenta) in NP-treated slice preparations. In short-time distribution following in vivo NP-administration, all organs contained carboxylated-nanoparticles, while PEGylated-nanoparticles were not detected in the brain and the placenta. Importantly, nanoparticles were not found in any embryonic tissues or in the barrier-protected brain parenchyma. Four days after the administration, particles were completely cleared from both the brain and the placenta, while PEGylated-, but not carboxylated-nanoparticles, were stuck in the kidney glomerular interstitium. In the spleen, macrophages accumulated large amount of carboxylated and PEGylated nanoparticles, with detectable redistribution from the marginal zone to the white pulp during the 4-day survival period. Conclusions: Spectral imaging fluorescence microscopy allowed detecting the tissue- and cell-type-specific accumulation and barrier-penetration of polystyrene nanoparticles with equal size but chemically distinct surfaces. The data revealed that polystyrene nanoparticles are retained by the reticuloendothelial system regardless of surface functionalization. Taken together with the increasing production and use of nanoparticles, the results highlight the necessity of long-term distribution studies to estimate the potential health-risks implanted by tissue-specific nanoparticle accumulation and clearance. © 2016 The Author(s).

  • Galvanic Replacement onto Complex Metal-Oxide Nanoparticles: Impact of Water or Other Oxidizers in the Formation of either Fully Dense Onion-like or Multicomponent Hollow MnOx/FeOx Structures

    López-Ortega A., Roca A.G., Torruella P., Petrecca M., Estradé S., Peiró F., Puntes V., Nogués J. Chemistry of Materials; 28 (21): 8025 - 8031. 2016. 10.1021/acs.chemmater.6b03765. IF: 9.407

    Multicomponent metal-oxide nanoparticles are appealing structures from applied and fundamental viewpoints. The control on the synthetic parameters in colloidal chemistry allows the growth of complex nanostructures with novel morphologies. In particular, the synthesis of biphase metal-oxide hollow nanoparticles has been reported based on galvanic replacement using an organic-based seeded-growth approach, but with the presence of H2O. Here we report a novel route to synthesize either fully dense or hollow core/shell metal-oxide nanoparticles (MnOx/FeOx) by simply adding or not oxidants in the reaction. We demonstrate that the presence of oxidants (e.g., O2 carried by the not properly degassed H2O or (CH3)3NO) allows the formation of hollow structures by a galvanic reaction between the MnOx and FeOx phases. In particular, the use of (CH3)3NO as oxidant allows for the first time a very reliable all-organic synthesis of hollow MnOx/FeOx nanoparticles without the need of water (with a somewhat unreliable oxidation role). Oxidants permit the formation of MnOx/FeOx hollow nanoparticles by an intermediate step where the MnO/Mn3O4 seeds are oxidized into Mn3O4, thus allowing the Mn3+ → Mn2+ reduction by the Fe2+ ions. The lack of proper oxidative conditions leads to full-dense onion-like core/shell MnO/Mn3O4/Fe3O4 particles. Thus, we show that the critical step for galvanic replacement is the proper seed oxidation states so that their chemical reduction by the shell ions is thermodynamically favored. © 2016 American Chemical Society.

  • Gold nanoparticles against cancer

    Comenge J., Romero F., Conill A., Puntes V.F. Handbook of Clinical Nanomedicine: Nanoparticles, Imaging, Therapy and Clinical Applications; 1: 1293 - 1314. 2016. 10.4032/9789814669214.

    [No abstract available]

  • Influence of Nanomaterial Compatibilization Strategies on Polyamide Nanocomposites Properties and Nanomaterial Release during the Use Phase

    Fernández-Rosas E., Vilar G., Janer G., González-Gálvez D., Puntes V., Jamier V., Aubouy L., Vázquez-Campos S. Environmental Science and Technology; 50 (5): 2584 - 2594. 2016. 10.1021/acs.est.5b05727. IF: 5.393

    The incorporation of small amounts of nanofillers in polymeric matrices has enabled new applications in several industrial sectors. The nanofiller dispersion can be improved by modifying the nanomaterial (NM) surface or predispersing the NMs to enhance compatibility. This study evaluates the effect of these compatibilization strategies on migration/release of the nanofiller and transformation of polyamide-6 (PA6), a thermoplastic polymer widely used in industry during simulated outdoors use. Two nanocomposites (NCs) containing SiO2 nanoparticles (NPs) with different surface properties and two multiwalled carbon nanotube (MWCNT) NCs obtained by different addition methods were produced and characterized, before and after accelerated wet aging conditions. Octyl-modified SiO2 NPs, though initially more aggregated than uncoated SiO2 NPs, reduced PA6 hydrolysis and, consequently, NM release. Although no clear differences in dispersion were observed between the two types of MWCNT NCs (masterbatch vs direct addition) after manufacture, the use of the MWCNT masterbatch reduced PA6 degradation during aging, preventing MWCNT accumulation on the surface and further release or potential exposure by direct contact. The amounts of NM released were lower for MWCNTs (36 and 108 mg/m2) than for SiO2 NPs (167 and 730 mg/m2), being lower in those samples where the NC was designed to improve the nanofiller-matrix interaction. Hence, this study shows that optimal compatibilization between NM and matrix can improve NC performance, reducing polymer degradation and exposure and/or release of the nanofiller. © 2016 American Chemical Society.

  • Interaction of gold nanoparticles and nickel(II) sulfate affects dendritic cell maturation

    Deville S., Baré B., Piella J., Tirez K., Hoet P., Monopoli M.P., Dawson K.A., Puntes V.F., Nelissen I. Nanotoxicology; 10 (10): 1395 - 1403. 2016. 10.1080/17435390.2016.1221476. IF: 7.913

    Despite many investigations have focused on the pristine toxicity of gold nanoparticles (GNPs), little is known about the outcome of co-exposure and interaction of GNPs with heavy metals which can possibly detoxify or potentiate them. Here, the combined exposure of nickel (II) sulfate (NiSO4) and GNPs on the maturation response of dendritic cells (DCs) was explored. Exposure to GNPs or NiSO4 separately induced cell activation. When cells were exposed to a mixture of both, however, the observed cell activation pattern indicated a competitive rather than an additive effect of both inducers with levels similar to those induced by NiSO4 alone. Quantification of the GNP uptake by DCs demonstrated a significant decrease in intracellular gold content during co-incubation with NiSO4. An extensive physiochemical characterization was performed to determine the interaction between GNPs and NiSO4 in the complex physiological media using nanoparticle tracking analyses, disc centrifugation, UV–visible spectroscopy, ICP-MS analyses, zeta potential measurements, electron microscopy, and proteomics. Although GNPs and NiSO4 did not directly interact with each other, the presence of NiSO4 in the physiological media resulted in changes in GNPs' charge and their associated protein corona (content and composition), which may contribute to a decreased cellular uptake of GNPs and sustaining the nickel-induced DC maturation. The presented results provide new insights in the interaction of heavy metals and NPs in complex physiological media. Moreover, this study highlights the necessity of mixture toxicology, since these combined exposures are highly relevant for human subjection to NPs and risk assessment of nanomaterials. © 2016 Informa UK Limited, trading as Taylor & Francis Group.

  • One-pot polyol synthesis of highly monodisperse short green silver nanorods

    Patarroyo J., Genç A., Arbiol J., Bastús N.G., Puntes V. Chemical Communications; 52 (73): 10960 - 10963. 2016. 10.1039/c6cc04796c. IF: 6.567

    Green silver nanorods (Ag NRs) of a low aspect ratio (2.8) have been produced in high yields via an optimized, simple, and robust one-pot polyol method in the presence of tannic acid, which favors the nucleation of decahedral seeds needed for the production of monodisperse Ag NRs. These Ag NRs were further used as sacrificial templates to produce Au hollow nanostructures via galvanic replacement reaction with HAuCl4 at room temperature. © 2016 The Royal Society of Chemistry.

  • Properties of silver nanoparticles influencing their uptake in and toxicity to the earthworm Lumbricus rubellus following exposure in soil

    Makama S., Piella J., Undas A., Dimmers W.J., Peters R., Puntes V.F., van den Brink N.W. Environmental Pollution; 218: 870 - 878. 2016. 10.1016/j.envpol.2016.08.016. IF: 4.839

    Physicochemical properties of nanoparticles influence their environmental fate and toxicity, and studies investigating this are vital for a holistic approach towards a comprehensive and adequate environmental risk assessment. In this study, we investigated the effects of size, surface coating (charge) of silver nanoparticles (AgNPs) – a most commonly-used nanoparticle-type, on the bioaccumulation in, and toxicity (survival, growth, cocoon production) to the earthworm Lumbricus rubellus. AgNPs were synthesized in three sizes: 20, 35 and 50 nm. Surface-coating with bovine serum albumin (AgNP_BSA), chitosan (AgNP_Chit), or polyvinylpyrrolidone (AgNP_PVP) produced negative, positive and neutral particles respectively. In a 28-day sub-chronic reproduction toxicity test, earthworms were exposed to these AgNPs in soil (0–250 mg Ag/kg soil DW). Earthworms were also exposed to AgNO3 at concentrations below known EC50. Total Ag tissue concentration indicated uptake by earthworms was generally highest for the AgNP_BSA especially at the lower exposure concentration ranges, and seems to reach a plateau level between 50 and 100 mg Ag/kg soil DW. Reproduction was impaired at high concentrations of all AgNPs tested, with AgNP_BSA particles being the most toxic. The EC50 for the 20 nm AgNP_BSA was 66.8 mg Ag/kg soil, with exposure to <60 mg Ag/kg soil already showing a decrease in the cocoon production. Thus, based on reproductive toxicity, the particles ranked: AgNP_BSA (negative) > AgNP_PVP (neutral) > Chitosan (positive). Size had an influence on uptake and toxicity of the AgNP_PVP, but not for AgNP_BSA nor AgNP_Chit. This study provides essential information on the role of physicochemical properties of AgNPs in influencing uptake by a terrestrial organism L. rubellus under environmentally relevant conditions. It also provides evidence of the influence of surface coating (charge) and the limited effect of size in the range of 20–50 nm, in driving uptake and toxicity of the AgNPs tested. © 2016 Elsevier Ltd

  • Quantifying the Sensitivity of Multipolar (Dipolar, Quadrupolar, and Octapolar) Surface Plasmon Resonances in Silver Nanoparticles: The Effect of Size, Composition, and Surface Coating

    Bastús N.G., Piella J., Puntes V. Langmuir; 32 (1): 290 - 300. 2016. 10.1021/acs.langmuir.5b03859. IF: 3.993

    The effect of composition, size, and surface coating on the sensitivity of localized multipolar surface plasmon resonances has been spectroscopically investigated in high-quality silver colloidal solutions with precisely controlled sizes from 10 to 220 nm and well-defined surface chemistry. Surface plasmon resonance modes have been intensively characterized, identifying the size-dependence of dipolar, quadrupolar, and octapolar modes. Modifications of the NP's surface chemistry revealed the higher sensitivity of large sizes, long molecules, thiol groups, and low-order resonance modes. We also extend this study to gold nanoparticles, aiming to compare the sensitivity of both materials, quantifying the higher sensitivity of silver. © 2015 American Chemical Society.

  • Size-Controlled Synthesis of Sub-10-nanometer Citrate-Stabilized Gold Nanoparticles and Related Optical Properties.

    Piella J., Bastús N.G., Puntes V. Chemistry of Materials; 28 (4): 1066 - 1075. 2016. 10.1021/acs.chemmater.5b04406. IF: 9.407

    Highly monodisperse, biocompatible and functionalizable sub-10-nm citrate-stabilized gold nanoparticles (Au NPs) have been synthesized following a kinetically controlled seeded-growth strategy. The use of traces of tannic acid together with an excess of sodium citrate during nucleation is fundamental in the formation of a high number (7 × 1013 NPs/mL) of small ∼3.5 nm Au seeds with a very narrow distribution. A homogeneous nanometric growth of these seeds is then achieved by adjusting the reaction parameters: pH, temperature, sodium citrate concentration and gold precursor to seed ratio. We use this method to produce Au NPs with a precise control over their sizes between 3.5 and 10 nm and a versatile surface chemistry allowing studying the size-dependent optical properties in this transition size regime lying between clusters and nanoparticles. Interestingly, an inflection point is observed for Au NPs smaller than 8 nm in which the sensitivity of the localized surface plasmon resonance (LSPR) peak position as a function of NPs size and surface modifications dramatically increase. These studies are relevant in the design of the final selectivity, activity and compatibility of Au NPs, especially in those (bio)applications where size is a critical parameter (e.g., biodistribution, multiplex labeling, and protein interaction). © 2016 American Chemical Society.

  • Toxicity of nickel in the marine calanoid copepod Acartia tonsa: Nickel chloride versus nanoparticles

    Zhou C., Vitiello V., Casals E., Puntes V.F., Iamunno F., Pellegrini D., Changwen W., Benvenuto G., Buttino I. Aquatic Toxicology; 170: 1 - 12. 2016. 10.1016/j.aquatox.2015.11.003. IF: 3.557

    Nickel compounds are widely used in industries and have been massively introduced in the environment in different chemical forms. Here we report the effect of two different chemical forms of nickel, NiCl2 and nickel nanoparticles (NiNPs), on the reproduction of the marine calanoid copepod Acartia tonsa. The behavior of nickel nanoparticles was analyzed with different techniques and with two protocols. In the "sonicated experiment" (SON) NiNP solution was sonicated while in the "non-sonicated experiment" (NON-SON) the solution was vigorously shaken by hand. Final nominal concentrations of 5, 10 and 50mgL-1 and 1, 5 and 10mgL-1 NiNPs were used for the acute and semichronic tests, respectively. Nanoparticle size did not change over time except for the highest concentration of 50mgL-1 NiNPs, in which the diameter increased up to 843nm after 48h. The concentration of Ni dissolved in the water increased with NP concentration and was similar for SON and NON-SON solutions. Our results indicate that sonication does not modify toxicity for the copepod A. tonsa. Mean EC50 values were similar for NON-SON (20.2mgL-1) and SON experiments (22.14mgL-1) in the acute test. Similarly, no differences occurred between the two different protocols in the semichronic test, with an EC50 of 7.45mgL-1 and 6.97mgL-1 for NON-SON and SON experiments, respectively. Acute and semichronic tests, conducted exposing A. tonsa embryos to NiCl2 concentrations from 0.025 to 0.63mgL-1, showed EC50 of 0.164 and 0.039mgL-1, respectively. Overall, A. tonsa is more sensitive to NiCl2 than NiNPs with EC50 being one order of magnitude higher for NiNPs. Finally, we exposed adult copepods for 4 days to NiCl2 and NiNPs (chronic exposure) to study the effect on fecundity in terms of daily egg production and naupliar viability. Egg production is not affected by either form of nickel, whereas egg viability is significantly reduced by 0.025mgL-1 NiCl2 and by 8.5mgL-1 NiNPs. At NiNP concentration below the acute EC50 (17mgL-1) only 9% of embryos hatched after 4 days. Interestingly, the percentage of naupliar mortality (>6;82%) observed in the semichronic test at the nominal concentration of 10mgL-1 NiNPs corresponding to almost 0.10mgL-1 of dissolved Ni, was similar to that recorded at the same Ni salt concentration. Electron microscopical analyses revealed that A. tonsa adults ingest NiNPs and excrete them through fecal pellets. To the best of our knowledge, this is the first study investigating the toxicity of two different forms of Ni on the reproductive physiology of the copepod A. tonsa and showing the ability of the calanoid copepod to ingest nanoparticles from seawater. © 2015 Elsevier B.V.

  • Tuning the Plasmonic Response up: Hollow Cuboid Metal Nanostructures

    Genç A., Patarroyo J., Sancho-Parramon J., Arenal R., Duchamp M., Gonzalez E.E., Henrard L., Bastús N.G., Dunin-Borkowski R.E., Puntes V.F., Arbiol J. ACS Photonics; 3 (5): 770 - 779. 2016. 10.1021/acsphotonics.5b00667. IF: 5.404

    We report the fine-tuning of the localized surface plasmon resonances (LSPRs) from ultraviolet to near-infrared by nanoengineering the metal nanoparticle morphologies from solid Ag nanocubes to hollow AuAg nanoboxes and AuAg nanoframes. Spatially resolved mapping of plasmon resonances by electron energy loss spectroscopy (EELS) revealed a homogeneous distribution of highly intense plasmon resonances around the hollow nanostructures and the interaction, that is, hybridization, of inner and outer plasmon fields for the nanoframe. Experimental findings are accurately correlated with the boundary element method (BEM) simulations demonstrating that the homogeneous distribution of the plasmon resonances is the key factor for their improved plasmonic properties. As a proof of concept for these enhanced plasmonic properties, we show the effective label free sensing of bovine serum albumin (BSA) of single-walled AuAg nanoboxes in comparison with solid Au nanoparticles, demonstrating their excellent performance for future biomedical applications. © 2016 American Chemical Society.


  • Chitosan functionalisation of gold nanoparticles encourages particle uptake and induces cytotoxicity and pro-inflammatory conditions in phagocytic cells, as well as enhancing particle interactions with serum components

    Boyles M.S.P., Kristl T., Andosch A., Zimmermann M., Tran N., Casals E., Himly M., Puntes V., Huber C.G., Lütz-Meindl U., Duschl A. Journal of Nanobiotechnology; 13 (1, 84) 2015. 10.1186/s12951-015-0146-9. IF: 4.115

    Background: Gold nanoparticles (AuNPs) are a popular choice for use in medical and biomedical research applications. With suitable functionalisation AuNPs can be applied in drug delivery systems, or can aid in disease diagnosis. One such functionalisation is with chitosan, which enables efficient interaction and permeation of cellular membranes, providing an effective adjuvant. As both AuNPs and chitosan have been shown to have low toxicity and high biocompatibility their proposed use in nanomedicine, either individually or combined, is expanding. However, further toxicological and immunological assessments of AuNP-chitosan conjugates are still needed. Therefore, we have evaluated how AuNP functionalisation with chitosan can affect uptake, cytotoxicity, and immunological responses within mononuclear cells, and influence the interaction of AuNPs with biomolecules within a complex biofluid. The AuNPs used were negatively charged through citrate-coating, or presented either low or high positive charge through chitosan-functionalisation. Uptake by THP-1 cells was assessed via transmission electron microscopy and electron energy loss spectroscopy, pro-inflammatory responses by ELISA and qRT-PCR, and cell death and viability via lactate dehydrogenase release and mitochondrial activity, respectively. Interactions of AuNPs with protein components of a frequently used in vitro cell culture medium supplement, foetal calf serum, were investigated using mass spectrometry. Results: Although cells internalised all AuNPs, uptake rates and specific routes of intracellular trafficking were dependent upon chitosan-functionalisation. Accordingly, an enhanced immune response was found to be chitosan-functionalisation-dependent, in the form of CCL2, IL-1β, TNF-α and IL-6 secretion, and expression of IL-1β and NLRP3 mRNA. A corresponding increase in cytotoxicity was found in response to chitosan-coated AuNPs. Furthermore, chitosan-functionalisation was shown to induce an increase in unique proteins associating with these highly charged AuNPs. Conclusions: It can be concluded that functionalisation of AuNPs with the perceived non-toxic biocompatible molecule chitosan at a high density can elicit functionalisation-dependent intracellular trafficking mechanisms and provoke strong pro-inflammatory conditions, and that a high affinity of these NP-conjugates for biomolecules may be implicit in these cellular responses. © 2015 Boyles et al.

  • Enhanced reactivity of high-index surface platinum hollow nanocrystals

    González E., Merkoçi F., Arenal R., Arbiol J., Esteve J., Bastús N.G., Puntes V. Journal of Materials Chemistry A; 4 (1): 200 - 208. 2015. 10.1039/c5ta07504a. IF: 7.443

    The precise morphological control of the surface of inorganic nanocrystals (NCs) is critical for the understanding of the unique properties of the materials at the nanoscale and useful in a wide range of applications, such as catalysis, where the development of highly active and low-cost materials represents a landmark for the development of industrial technologies. Here we show how combining solid state chemistry and colloidal synthesis allows us to prepare exotic materials, in particular, PtAg@Pt single-crystal hollow NCs with high-index planes synthesized at room temperature by controlled corrosion of silver templates, which minimize Pt consumption and maximize surface reactivity. © The Royal Society of Chemistry 2016.

  • Exploring new synthetic strategies for the production of advanced complex inorganic nanocrystals

    Bastús N.G., Gonzalez E., Esteve J., Piella J., Patarroyo J., Merkoçi F., Puntes V. Zeitschrift fur Physikalische Chemie; 229 (1-2): 65 - 83. 2015. 10.1515/zpch-2014-0611. IF: 1.356

    The design of new protocols for the colloidal synthesis of complex nanocrystals (NCs) with advanced functionalities, comprising both hybrid and hollow structures, and the study of their fundamental properties is of paramount importance for the development of a new generation of nanostructured materials. The possibility of tailoring the dimensional regime of NCs, along with its composition and structure, represents a landmark achievement in the control of their unique physico-chemical properties. These properties, alongside with the ability to cheaply produce high quality NCs in fairly large amounts by wet-chemistry techniques, leads to their potential applicability from materials science to nanomedicine. Within this context, this review is focused on describing a successful framework for designing synthetic strategies for the production of advanced complex NCs, integrating the development of new synthetic methods with its structural characterization, monitoring of their properties, and study of its reactivity. As a result, it is expected to provide new routes to produce robust and easy-to-process NCs in a wide range of sizes, shapes and configurations that can be explored to achieve the combination of all degrees of control, aiming to produce a complete and diverse library of material combinations that will expand its applicability in a wide diversity of fields. © 2014 Walter de Gruyter Berlin/Boston.

  • High aspect ratio gold nanorods grown with platinum seeds

    Varón M., Arbiol J., Puntes V.F. Journal of Physical Chemistry C; 119 (21): 11818 - 11825. 2015. 10.1021/acs.jpcc.5b01263. IF: 4.772

    Using Au chloride as precursor, Pt nanocrystals as seeds, ascorbic acid as a reducer, and CTAB as surfactant and complexing agent, extremely long Au nanorods have been grown. The influence of different parameters such as the composition of the seeds, the amount of Pt, or the type of Pt present in solution has been analyzed. These large Au NRs have been exhaustively characterized by (S)TEM, SEM and optical microscopy as well as UV-vis spectroscopy and their morphology correlated with the growth mechanism. © 2015 American Chemical Society.

  • Longitudinal domain wall formation in elongated assemblies of ferromagnetic nanoparticles

    Varón M., Beleggia M., Jordanovic J., Schiøtz J., Kasama T., Puntes V.F., Frandsen C. Scientific Reports; 5 ( 14536) 2015. 10.1038/srep14536. IF: 5.578

    Through evaporation of dense colloids of ferromagnetic ∼13â €‰nm Co particles onto carbon substrates, anisotropic magnetic dipolar interactions can support formation of elongated particle structures with aggregate thicknesses of 100-400â €‰nm and lengths of up to some hundred microns. Lorenz microscopy and electron holography reveal collective magnetic ordering in these structures. However, in contrast to continuous ferromagnetic thin films of comparable dimensions, domain walls appear preferentially as longitudinal, i.e., oriented parallel to the long axis of the nanoparticle assemblies. We explain this unusual domain structure as the result of dipolar interactions and shape anisotropy, in the absence of inter-particle exchange coupling.

  • Optimising the use of commercial LAL assays for the analysis of endotoxin contamination in metal colloids and metal oxide nanoparticles

    Li Y., Italiani P., Casals E., Tran N., Puntes V.F., Boraschi D. Nanotoxicology; 9 (4): 462 - 473. 2015. 10.3109/17435390.2014.948090. IF: 3.821

    Engineered nanoparticles (NP) are generally contaminated by bacterial endotoxin, a ubiquitous bacterial molecule with significant toxic and inflammatory effects. The presence of endotoxin, if not recognised, can be responsible for many of the in vitro and in vivo effects attributed to NPs. The Limulus Amoebocyte Lysate (LAL) assay, the test requested by regulatory authorities for assessing endotoxin contamination in products for human use, is not immediately applicable for testing endotoxin in NP preparations, mainly due to the possible interference of NPs with the assay readouts and components. In this study, we have compared different commercially available LAL assays for detecting endotoxin in gold, silver and iron oxide NPs. Different NP chemistry, concentrations and surface coatings could differently interfere with the LAL assays' results. After accurate testing of the possible interaction/interference of NPs with the various assay components, the modified chromogenic LAL assay proved the most suitable assay for measuring endotoxin in NP samples, provided the appropriate controls are performed. Thus, endotoxin determination can be performed in NP preparation with commercial LAL assays only after assay validation, i.e. once possible interference of NPs with the assay components and readouts has been excluded. © 2014 Informa UK Ltd. All rights reserved: reproduction in whole or part not permitted.

  • SERS efficiencies of micrometric polystyrene beads coated with gold and silver nanoparticles: The effect of nanoparticle size

    Mir-Simon B., Morla-Folch J., Gisbert-Quilis P., Pazos-Perez N., Xie H.-N., Bastús N.G., Puntes V., Alvarez-Puebla R.A., Guerrini L. Journal of Optics (United Kingdom); 17 (11, 114012) 2015. 10.1088/2040-8978/17/11/114012. IF: 2.059

    Rapid advances in nanofabrication techniques of reproducibly manufacturing plasmonic substrates with well-defined nanometric scale features and very large electromagnetic enhancements paved the way for the final translation of the analytical potential of surface-enhanced Raman scattering (SERS) to real applications. A vast number of different SERS substrates have been reported in the literature. Among others, discrete particles consisting of an inorganic micrometric or sub-micrometric core homogeneously coated with plasmonic nanoparticles stand out for their ease of fabrication, excellent SERS enhancing properties, long-term optical stability and remarkable experimental flexibility (manipulation, storage etc). In this article, we performed a systematic experimental study of the correlation between the size of quasi-spherical gold and silver nanoparticle and the final optical property of their corresponding assembles onto micrometric polystyrene (PS) beads. The size and composition of nanoparticles play a key role in tuning the SERS efficiency of the hybrid material at a given excitation wavelength. This study provides valuable information for the selection and optimization of the appropriate PS@NPs substrates for the desired applications. © 2015 IOP Publishing Ltd.

  • The oxidative potential of differently charged silver and gold nanoparticles on three human lung epithelial cell types

    Schlinkert P., Casals E., Boyles M., Tischler U., Hornig E., Tran N., Zhao J., Himly M., Riediker M., Oostingh G.J., Puntes V., Duschl A. Journal of Nanobiotechnology; 13 (1, 1) 2015. 10.1186/s12951-014-0062-4. IF: 4.115

    Background: Nanoparticle (NPs) functionalization has been shown to affect their cellular toxicity. To study this, differently functionalized silver (Ag) and gold (Au) NPs were synthesised, characterised and tested using lung epithelial cell systems. Methods: Monodispersed Ag and Au NPs with a size range of 7 to 10 nm were coated with either sodium citrate or chitosan resulting in surface charges from -50 mV to +70 mV. NP-induced cytotoxicity and oxidative stress were determined using A549 cells, BEAS-2B cells and primary lung epithelial cells (NHBE cells). TEER measurements and immunofluorescence staining of tight junctions were performed to test the growth characteristics of the cells. Cytotoxicity was measured by means of the CellTiter-Blue ® and the lactate dehydrogenase assay and cellular and cell-free reactive oxygen species (ROS) production was measured using the DCFH-DA assay. Results: Different growth characteristics were shown in the three cell types used. A549 cells grew into a confluent mono-layer, BEAS-2B cells grew into a multilayer and NHBE cells did not form a confluent layer. A549 cells were least susceptible towards NPs, irrespective of the NP functionalization. Cytotoxicity in BEAS-2B cells increased when exposed to high positive charged (+65-75 mV) Au NPs. The greatest cytotoxicity was observed in NHBE cells, where both Ag and Au NPs with a charge above +40 mV induced cytotoxicity. ROS production was most prominent in A549 cells where Au NPs (+65-75 mV) induced the highest amount of ROS. In addition, cell-free ROS measurements showed a significant increase in ROS production with an increase in chitosan coating. Conclusions: Chitosan functionalization of NPs, with resultant high surface charges plays an important role in NP-toxicity. Au NPs, which have been shown to be inert and often non-cytotoxic, can become toxic upon coating with certain charged molecules. Notably, these effects are dependent on the core material of the particle, the cell type used for testing and the growth characteristics of these cell culture model systems. © Schlinkert et al.

  • Use of cerium oxide (CeO2) nanoparticles for the adsorption of dissolved cadmium (II), lead (II) and chromium (VI) at two different pHs in single and multi-component systems

    Contreras A.R., Casals E., Puntes V., Komilis D., Sánchez A., Font X. Global Nest Journal; 17 (3): 536 - 543. 2015. . IF: 0.468

    Cerium oxide (CeO2) nanoparticles (NPs) were used for the removal of cadmium (II), lead (II) and chromium (VI) ions in single aqueous solutions and in solutions with mixtures of the three metals. The adsorption studies were carried out at pH 5 and 7 using a systematic factorial experimental design that considered the metal concentration from 1 mg l-1 to 10 mg l-1 and NP concentration from 0.064 g l-1 to 0.640 g l-1. The highest adsorption capacity was obtained in the removal of lead (II) (128.1 mg g-1), followed by cadmium (II) (93.4 mg g-1) and finally chromium (VI) (34.4 mg g-1). Data were fitted to a polynomial function obtaining the best reduced models. The type of system (single, multi-component) did not affect sorption capacity, whilst pH affected the sorption of Cd and Cr, but not that of lead. CeO2 nanoparticles proved to be effective adsorbents in removing all three heavy metals in multi-component systems, which opens a new window for their use as sorbent materials in complex waters contaminated with mixtures of heavy metals. © 2015 Global NEST Printed in Greece. All rights reserved.


  • Common strategies and technologies for the ecosafety assessment and design of nanomaterials entering the marine environment

    Corsi, I.; Cherr, G.N.; Lenihan, H.S.; Labille, J.; Hassellov, M.; Canesi, L.; Dondero, F.; Frenzilli, G.; Hristozov, D.; Puntes, V.; Della Torre, C.; Pinsino, A.; Libralato, G.; Marcomini, A.; Sabbioni, E.; Matranga, V. ACS Nano; 8 (10): 9694 - 9709. 2014. 10.1021/nn504684k. IF: 12.033

  • Gene expression profiles reveal distinct immunological responses of cobalt and cerium dioxide nanoparticles in two in vitro lung epithelial cell models

    Verstraelen, S.; Remy, S.; Casals, E.; De Boever, P.; Witters, H.; Gatti, A.; Puntes, V.; Nelissen, I. Toxicology Letters; 228 (3): 157 - 169. 2014. 10.1016/j.toxlet.2014.05.006. IF: 3.355

  • Interaction of differently functionalized fluorescent silica nanoparticles with neural stem- and tissue-type cells

    Izak-Nau, E.; Kenesei, K.; Murali, K.; Voetz, M.; Eiden, S.; Puntes, V.F.; Duschl, A.; Madarász, E. Nanotoxicology; 8 (SUPPL. 1): 138 - 148. 2014. 10.3109/17435390.2013.864427. IF: 7.336

  • Little Adjustments Significantly Improve the Turkevich Synthesis of Gold Nanoparticles

    Schulz, F.; Homolka, T.; Bastús, NG.; Puntes, V. F.; Weller,H.; Vossmeyer, T. Langmuir : the ACS journal of surfaces and colloids; 30 (35): 10779 - 10784. 2014. 10.1021/la503209b. IF: 4.384

  • Nanoparticles for imaging, sensing, and therapeutic intervention

    Bogart, L.K.; Pourroy, G.; Murphy, C.J.; Puntes, V.; Pellegrino, T.; Rosenblum, D.; Peer, D.; Lévy, R. ACS Nano; 8 (4): 3107 - 3122. 2014. 10.1021/nn500962q. IF: 12.033

  • Optimising the use of commercial LAL assays for the analysis of endotoxin contamination in metal colloids and metal oxide nanoparticles.

    Li, Y.; Italiani, P.; Casals, E.; Tran, N.; Puntes, V. F.; Boraschi, D. Nanotoxicology; 14: 1 - 12. 2014. . IF: 7.336

  • Programmed iron oxide nanoparticles disintegration in anaerobic digesters boosts biogas production

    Casals, E.; Barrena, R.; García, A.; González, E.; Delgado, L.; Busquets-Fité, M.; Font, X.; Arbiol, J.; Glatzel, P.; Kvashnina, K.; Sánchez, A.; Puntes, V. Small; 10 (14): 2801 - 2808. 2014. 10.1002/smll.201303703. IF: 7.514

  • Synthesis of highly monodisperse citrate-stabilized silver nanoparticles of up to 200 nm: Kinetic control and catalytic properties

    Bastús, N.G.; Merkoçi, F.; Piella, J.; Puntes, V. Chemistry of Materials; 26 (9): 2836 - 2846. 2014. 10.1021/cm500316k. IF: 8.535


  • Absence of Ce3+ sites in chemically active colloidal ceria nanoparticles

    Cafun, J.-D.; Kvashnina, K.O.; Casals, E.; Puntes, V.F.; Glatzel, P. ACS Nano; 7 (12): 10726 - 10732. 2013. 10.1021/nn403542p. IF: 12.062

  • Altered characteristics of silica nanoparticles in bovine and human serum: the importance of nanomaterial characterization prior to its toxicological evaluation

    Izak-Nau, E.; Voetz, M.; Eiden, S.; Duschl, A.; Puntes, V.F. Particle and Fibre Toxicology; 2013. 10.1186/1743-8977-10-56. IF: 9.178

  • Characterizing Nanoparticles Reactivity: Structure-Photocatalytic Activity Relationship

    Piella, J.; Bastús, N. G.; Casals, E.; Puntes, V. Journal of Physics: Conference Series; 429: 1. 2013. 10.1088/1742-6596/429/1/012040. IF: 0.000

  • Dipolar magnetism in ordered and disordered low-dimensional nanoparticle assemblies

    Varón, M.; Beleggia, M.; Kasama, T.; Harrison, R.J.; Dunin-Borkowski, R.E.; Puntes, V.F.; Frandsen, C. Scientific Reports; 2013. 10.1038/srep01234. IF: 2.927

  • Engineered Inorganic Nanoparticles for Drug Delivery Applications

    Ojea-Jiménez, I.; Comenge, J.; García-Fernández, L.; Megson, Z.A.; Casals, E.; Puntes, V.F. Current Drug Metabolism; 14 (5): 518 - 530. 2013. 10.2174/13892002113149990008. IF: 4.405

  • Exploring release and recovery of nanomaterials from commercial polymeric nanocomposites

    Busquets-Fité, M.; Fernandez, E.; Janer, G.; Vilar, G.; Vázquez-Campos, S.; Zanasca, R.; Citterio, C.; Mercante, L.; Puntes, V. Journal of Physics: Conference Series; 429: 1. 2013. 10.1088/1742-6596/429/1/012048. IF: 0.000

  • Monitoring migration and transformation of nanomaterials in polymeric composites during accelerated aging

    Vilar, G.; Fernández-Rosas, E.; Puntes, V.; Jamier, V.; Aubouy, L.; & Vázquez-Campos, S Journal of Physics: Conference Series; 429: 2. 2013. 10.1088/1742-6596/429/1/012044. IF: 0.000

  • Radiochemical synthesis of105gAg-labelled silver nanoparticles

    Ichedef, C.; Simonelli, F.; Holzwarth, U.; Bagaria, J.P.; Puntes, V.F.; Cotogno, G.; Gilliland, D.; Gibson, N. Journal of Nanoparticle Research; 15 (11) 2013. 10.1007/s11051-013-2073-8. IF: 2.175

  • Spontaneous formation of hollow cobalt oxide nanoparticles by the Kirkendall effect at room temperature at the water-air interface

    Varón, M.; Ojea-Jimenez, I.; Arbiol, J.; Balcells, L.; Martínez, B.; Puntes, V.F. Nanoscale; 5: 2429 - 2436. 2013. 10.1039/c2nr32657d. IF: 6.233

  • Stability of polymer encapsulated quantum dots in cell culture media

    Ojea-Jiménez, I.; Piella, J.; Nguyen, T. L.; Bestetti, A.; Ryan, A. D.; Puntes, V. Journal of Physics: Conference Series; 429: 3. 2013. 10.1088/1742-6596/429/1/012009. IF: 0.000

  • The social context of nanotechnology and regulating its uncertainty: A nanotechnologist approach

    Jamier, V.; Gispert, I.; Puntes, V. Journal of Physics: Conference Series; 429: 4. 2013. 10.1088/1742-6596/429/1/012059. IF: 0.000


  • Citrate-Coated Gold Nanoparticles As Smart Scavengers for Mercury(II) Removal from Polluted Waters

    Ojea-Jiménez, I.; López, X.; Arbiol, J.; Puntes, V. ACS Nano; 6: 2253 - 2260. 2012. .

  • Controlled positioning of nanoparticles on graphene by noninvasive AFM lithography

    Bellido, E.; Ojea-Jiménez, I.; Ghirri, A.; Alvino, C.; Candini, A.; Puntes, V.; Affronte, M.; Domingo, N.; Ruiz-Molina, D. Langmuir : the ACS journal of surfaces and colloids; 28: 12400 - 12409. 2012. 10.1021/la3023419.

  • Detoxifying Antitumoral Drugs via Nanoconjugation: The Case of Gold Nanoparticles and Cisplatin

    Comenge, J.; Sotelo, C.; Romero, F.; Gallego, O.; Barnadas, A.; García-Caballero Parada, T.; Domínguez, F.; Puntes, V.F. Plos One. Open acces; 7(10): e47562. 2012. .

  • Effect of cerium dioxide, titanium dioxide, silver, and gold nanoparticles on the activity of microbial communities intended in wastewater treatment.

    García, A.; Delgado, L.;Torà, JA.; Casals, E.; González, E.; Puntes, V.; Font, X.; Carrera, J.; Sánchez, A. Journal of Hazardous Materials; 199-200: 64 - 72. 2012. 10.1016/j.jhazmat.2011.10.057.

  • Engineered nonviral nanocarriers for intracellular gene delivery applications

    Ojea-Jiménez, I.; Tort, O.; Lorenzo, J.; Puntes, V.F. Biomedical materials (Bristol, England); 7(5): 54106. 2012. 10.1088/1748-6041/7/5/054106.

  • Facile Preparation of Cationic Gold Nanoparticle-Bioconjugates for Cell Penetration and Nuclear Targeting

    Ojea-Jiménez, I.; García-Fernández, L.; Lorenzo, J.; Puntes, V. F. ACS Nano; 6 (9): 7692 - 7702. 2012. .

  • Inorganic nanoparticle biomolecular corona: Formation, evolution and biological impact

    Casals, E.; Puntes, V.F. Nanomedicine; 7: 1917 - 1930. 2012. 10.2217/nnm.12.169.

  • Inorganic nanoparticles and the environment: Balancing benefits and risks

    Casals, E.; González, E.; Puntes, V. Comprehensive Analytical Chemistry; 59: 265 - 290. 2012. 10.1016/B978-0-444-56328-6.00008-6.

  • Inorganic nanoparticles and the immune system: detection, selective activation and tolerance.

    Bastús, N.G.; Sánchez-Tilló, E.; Pujals, S.; Comenge, J.; Giralt, E.; Celada, A.; Lloberas, J.; Puntes, V.F. Proceedings of SPIE - The International Society for Optical Engineering; 823217: 1. 2012. 10.1117/12.917327.

  • Physicochemical Characteristics of Protein¿NP Bioconjugates: The Role of Particle Curvature and Solution Conditions on Human Serum Albumin Conformation and Fibrillogenesis Inhibition

    Goy-López, S.; Juárez, J.; Alatorre-Meda, M.; Casals, E.; Puntes, V.F.; Taboada, P.; Mosquera, V. Langmuir : the ACS journal of surfaces and colloids; 28(24): 9113 - 9126. 2012. 10.1021/la300402w.

  • Potential use of CeO2 , TiO2 and Fe3O4 nanoparticles for the removal of cadmium from water

    Contreras, A.R.; García, A.; González, E.; Casals, E.; Puntes, V.F.; Sánchez, A.; Fonta, X.; Recillas, S. Desalination and Water Treatment; 41 (1-3): 296 - 300. 2012. 10.1080/19443994.2012.664743.

  • Preliminary study of phosphate adsorption onto cerium oxide nanoparticles for use in water purification; nanoparticles synthesis and characterization

    Recillas, S.; García, A.; González, E.; Casals, E.; Puntes, V.F.; Sánchez, A.; Font, X. Water Science and Technology; 66(3): 503 - 509. 2012. 10.2166/wst.2012.185.

  • Rational nanoconjugation improves biocatalytic performance of enzymes: Aldol addition catalyzed by immobilized rhamnulose-1-phosphate aldolase

    Ardao, I.; Comenge, J.; Benaiges, M.D.; Álvaro, G.; Puntes, V.F. Langmuir : the ACS journal of surfaces and colloids; 28: 6461 - 6467. 2012. 10.1021/la3003993.

  • Reactivity of inorganic nanoparticles in biological environments: Insights into nanotoxicity mechanisms

    Casals, E.; Gonzalez, E.; Puntes, V.F. Journal of Physics D - Applied Physics; 45 2012. 10.1088/0022-3727/45/44/443001.

  • Synthesis of co-organosilane-Au nanocomposites via a controlled interphasic reduction

    Ojea-Jiménez, I.; Lorenzo, J.; Rebled, J.M.; Sendra, J.; Arbiol, J.; Puntes, V. Chemistry of Materials; 24: 4019 - 4027. 2012. 10.1021/cm300757j.


  • Acute toxicity of cerium oxide, titanium oxide and iron oxide nanoparticles using standardized tests

    García, A.; Espinosa, R.; Delgado, L.; Casals, E.; González, E.; Puntes, V.; Barata, C.; Font, X.; Sánchez, A.; Barata, C Desalination; 269: 136 - 141. 2011. 10.1016/j.desal.2010.10.052.

  • Analysis of time-dependent conjugation of gold nanoparticles with an antiparkinsonian molecule by using curve resolution methods

    Amigo, J.M.; Bastús, N.G.; Hoen, R.; Vázquez-Campos, S.; Varón, M.; Royo, M.; Puntes, V.F. Analytica Chimica Acta; 2011. .

  • Carving at the nanoscale: Sequential galvanic exchange and Kirkendall growth at room temperature

    González, E.; Arbiol, J.; Puntes, V.F. SCIENCE; 334: 1377 - 1380. 2011. 10.1126/science.1212822.

  • Ecotoxicity of, and remediation with, engineered inorganic nanoparticles in the environment

    Sánchez, A.; Recillas, S.; Font, X.; Casals, E.; González, E.; Puntes, V.F. TrAC - Trends in Analytical Chemistry; 2011. .

  • Hardening of the nanoparticle-protein corona in metal (Au, Ag) and oxide (Fe 3O 4, CoO, and CeO 2) nanoparticles

    Casals, E.; Pfaller, T.; Duschl, A.; Oostingh, G.J.; Puntes, V.F. Small; 7: 3479 - 3486. 2011. 10.1002/smll.201101511.

  • Influence of the Sequence of the Reagents Addition in the Citrate-Mediated Synthesis of Gold Nanoparticles

    Ojea-Jiménez, I.; Bastús, N.G.; Puntes, V.F. Journal of Physical Chemistry C; 2011. 10.1021/jp2017242.

  • Kinetically Controlled Seeded Growth Synthesis of Citrate-Stabilized Gold Nanoparticles of up to 200 nm: Size Focusing versus Ostwald Ripening

    Bastús, N.G.; Comenge, J.; Puntes, V.F. Langmuir : the ACS journal of surfaces and colloids; 2011. .

  • Large 2D self-assembled domains of cobalt nanoparticles onto silicon wafers

    Peña, L.; Varón, M.; Konstantinovic, Z.; Balcells, L.; Martínez, B.; Puntes, V. Journal of Materials Chemistry; 21: 16973 - 16977. 2011. 10.1039/c1jm11647a.

  • Nano-immunosafety: issues in assay validation

    Boraschi, D.; Oostingh, G.J.; Casals, E.; Italiani, P.; Nelissen, I.; Puntes, V.F:; Duschl, A. Journal of Physics: Conference Series; 2011. .

  • Nanoparticle microinjection and Raman spectroscopy as tools for nanotoxicology studies

    Candeloro, P.; Tirinato, L.; Malara, N.; Fregola, A.; Casals, E.; Puntes, V.; Perozziello, G.; Gentile, F.; Coluccio, M.L.; Das, G.; Liberale, C.; De Angelis, F.; Di Fabrizio, E. The Analyst; 2011. .

  • Problems and challenges in the development and validation of human cell-based assays to determine nanoparticle-induced immunomodulatory effects

    Oostingh, G.J.; Casals, E.; Italiani, P.; Colognato, R.; Stritzinger, R.; Ponti, J.; Pfaller, T.; Kohl, Y.; Ooms, D.; Favilli, F.; Leppens, H.; Lucchesi, D.; Rossi, F.; Nelissen, I.; Thielecke, H.; Puntes, V.F.; Duschl, A.; Boraschi, D. Particle and Fibre Toxicology; 2011. .

  • Pt nanocrystal evolution in the presence of Au(iii)-salts at room temperature: Spontaneous formation of AuPt heterodimers

    Lim, S.I.; Varon, M.; Ojea-Jiménez, I.; Arbiol, J.; Puntes, V. Journal of Materials Chemistry; 21: 11518 - 11523. 2011. 10.1039/c1jm10313j.

  • Synthesis and evaluation of gold nanoparticle -modified polyelectrolyte capsules under microwave irradiation for remotely controlled release for cargo

    del Mercato, L.L.; Gonzalez, E.; Abbasi, A.Z.; Parak, W.J.; Puntes, V.F. Journal of Materials Chemistry; 2011. .

  • Use of CeO2, TiO2 and Fe3O4 nanoparticles for the removal of lead from water: Toxicity of nanoparticles and derived compounds

    Recillas, S.; García, A.; González, E.; Casals, E.; Puntes, V.F.; Sánchez, A.; Font, X. Desalination; 2011. .


  • Chromium VI adsorption on cerium oxide nanoparticles and morphology changes during the process

    Recillas, S.; Colón, J.; Casals, E.; González, E.; Puntes, V.; Sánchez, A.; Font, X. Journal of Hazardous Materials; 2010. .

  • Coordination polymer particles as potential drug delivery systems

    Imaz, I.; Rubio-Martínez, M.; García-Fernández, L.; García, F.; Ruiz-Molina, D.; Hernando, J.; Puntes, V.; Maspoch, D. Chemical Communications; 46: 4737 - 4739. 2010. 10.1039/c003084h.

  • Correlating Physico-Chemical with Toxicological Properties of Nanoparticles: The Present and the Future

    Rivera Gil, P.; Oberdörster, G.; Elder, A.; Puntes, V.F.; Parak, W.J. ACS Nano; 2010. .

  • Dipolar driven spontaneous self assembly of superparamagnetic CO nanoparticles into micrometric rice-Grain like structures

    Varón, M.; Peña, L.; Balcells, L.; Skumryev, V.; Martinez, B.; Puntes, V. Langmuir : the ACS journal of surfaces and colloids; 26: 109 - 116. 2010. 10.1021/la902169s.

  • Exploring the limitations of the use of competing reducers to control the morphology and composition of Pt and PtCo nanocrystals

    Lim, S.I.; Varón, M.; Ojea-Jiménez, I.; Arbiol, J.; Puntes, V. Chemistry of Materials; 22: 4495 - 4504. 2010. 10.1021/cm101436p.

  • Small gold nanoparticles synthesized with sodium citrate and heavy water: Insights into the reaction mechanism

    Ojea-Jiménez, I.; Romero, F.M.; Bastús, N.G.; Puntes, V. Journal of Physical Chemistry C; 114: 1800 - 1804. 2010. 10.1021/jp9091305.

  • Synthesis of platinum cubes, polypods, cuboctahedrons, and raspberries assisted by cobalt nanocrystals

    Lim, S.I.; Ojea-Jiménez, I.; Varon, M.; Casals, E.; Arbiol, J.; Puntes, V. Nano Letters; 10: 964 - 973. 2010. 10.1021/nl100032c.

  • The suitability of different cellular in vitro immunotoxicity and genotoxicity methods for the analysis of nanoparticle-induced events

    Pfaller, T.; Colognato, R.; Nelissen, I.; Favilli, F.; Casals, E.; Ooms, D.; Leppens, H.; Ponti, J; Stritzinger, R.; Puntes, V.F.; Boraschi, D.; Duschl, A.; Oostingh, G.J. Nanotoxicology; 2010. 10.3109/17435390903374001.

  • Time evolution of the nanoparticle protein corona

    Casals, E.; Pfaer, T.; Dusch, A.; Oostingh, G.J.; Puntes, V.F. ACS Nano; 2010. .


  • Homogeneous Conjugation of Peptides onto Gold Nanoparticles Enhances Macrophage Response

    Bastús, N. G.; Sánchez-Tillo, E.; Pujals, S.; Farrera, C.; López, C. ; Giralt, E. ; Celanda, A. ; Lloberas, J.; Puntes, V. ACS Nano; 3 (6): 1335 - 1344. 2009. 10.1021/nn8008273 CCC: $40.75.

  • Identifying Spinel Phases in Nearly Monodisperse Iron Oxide Colloidal Nanocrystal

    Corrias, A.; Mountjoy, G.; Loche, D.; Puntes, V.; Falqui, A.; Zanella, M.; Parak, W.J.; Casula, M.F. Journal of the American Chemical Society; 113 (43): 18667. 2009. 10.1021/jp9047677 CCC: $40.75.

  • Impact of engineered nanoparticles on immune-related genes and processes in human alveolar epithelial cells

    Nelissen, I.; Verstraelen, S.; De Boever, P.; Casals, E.; Ooms, D.; Leppens, H.; Hollanders, K.; Van Den Heuvel, R.; Schoeters, G.; Puntes, V.; Witters, H. Toxicology Letters; 189: 186 - 189. 2009.

  • In vitro investigation of immunomodularoty effects caused by engineered inorganic nanoparticles- the impact of experimental design and cell choice

    Pfaller, T.; Puntes, V. F.; Casals, E.; Duschl, A.; Oostingh, G.J. Nanotoxicology; 3 (1): 46 - 59. 2009. 10.1016/j.toxlet.2009.06.649 .

  • Inorganic engineered nanoparticles and their impact on the immune response

    Sperling, R. A.; Casals, E.; Comenge, J.; Bastús, N. G. ; Puntes, V. Current Drug Metabolism; 10: 895 - 904. 2009.

  • Instability of Cationic Gold Nanoparticle Bioconjugates: The Role of Citrate Ions

    Ojea-Jimenez, I. ; Puntes, V. Journal of the American Chemical Society; 131 (37): 13320 - 133327. 2009. 10.1021/ja902894s.

  • Nano-cotton fabrics with high ultraviolet protection

    Roshan, P.; Bautista, L.; De la Varga, M .; Botet, J.M. ; Casals, E.; Puntes, V.F. ; Marsal, F. Textile Research Journal; 13: 101177. 2009. 10.1177/0040517509342316.

  • Nanopànic o Nanoeufòria?: Nanoinfo

    Puntes, V.F. ; Garcia Horn, A. Mètode; 63: 25 - 30. 2009. .

  • Peptides conjugated to gold nanoparticles induce macrophage activation

    Bastús, N. G.; Sánchez-Tillo, E.; Pujals, S.; Farrera, C.; Kogan, M. J.; Giralt, E.; Celada, A.; Lloberas, J.; Puntes, V. F. Molecular Immunology; 46 (4): 743 - 748. 2009. 10.1016/j.molimm.2008.08.277 .

  • Scientist still wondering-Industry are selling

    Gatti, A.; Puntes, V. Nano; 46 (4): 743 - 748. 2009. .

  • Shuttling Gold Nanoparticles into Tumoral Cells with an Amphipathic Proline-Rich Peptide

    Pujals, S. ; Bastus, N. G.; Pereiro, E.; López-Iglesias, C.; Puntes, V. F.; Kogan, M. J.; Giralt, E. Chemistry: a European Journal; 10 (6): 1025 - 1031. 2009. 10.1002/cbic.200800843 .


  • Distribution and potential toxicity of engineered inorganic nanoparticles and carbon nanostructures in biological systems

    Casals E.; Vazquez-Campos S.; Bastus N.G.; Puntes V. TrAC - Trends in Analytical Chemistry; 27 (8): 672 - 683. 2008. 10.1016/j.trac.2008.06.004.

  • Gold Nanoparticles and Microwave Irradiation Inhibit Beta-Amyloid Amyloidogenesis

    Araya Eyleen; Olmedo Ivonne; Bastus Neus G.; Guerrero Simon; Puntes Victor F.; Giralt Ernest; Kogan Marcelo J Nanoscale Research Letters; 3 (11): 435 - 443. 2008. 10.1007/s11671-008-9178-5.

  • Low-Temperature Synthesis of CoO Nanoparticles via Chemically Assisted Oxidative Decarbonylation

    Lagunas A.; Mairata i Payeras A.; Jimeno C.; Puntes V. F.; Pericàs M. A. Chemistry of Materials; 20 (1): 92 - 100. 2008. 10.1021/cm7018636.

  • Nanoparticles for cosmetics: how safe is safe?

    M. Guix-Noguera; C. Carbonell; J. Comenge; L. García-Fernández; A. Alarcón-Pardo; E. Casals; V. Puntes Contributions to Science; 4: 2. 2008. 10.2436/20.7010.01.52.

  • Reactivity of engineered inorganic nanoparticles and carbon nanostructures in biological media

    Neus G. Bastús; Eudald Casals; Socorro Vázquez-Campos; Victor Puntes Nanotoxicology; 2 (3): 99 - 112. 2008. 10.1080/17435390802217830.

  • Shuttling Gold Nanoparticles into Tumoral Cells with an Amphipathic Pro rich Peptide

    Pujals S; Bastús NG; Pereiro E; López-Iglesias E; Puntes VF; Kogan MJ; Giralt E Chemistry: a European Journal; 10: 1025 - 1031. 2008. 10.1002/cbic.200800843.