Staff directory
- ORCID: 0000-0002-9026-1743
Publications
2024
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First-in-human controlled inhalation of thin graphene oxide nanosheets to study acute cardiorespiratory responses
Andrews, Jack P M; Joshi, Shruti S; Tzolos, Evangelos; Syed, Maaz B; Cuthbert, Hayley; Crica, Livia E; Lozano, Neus; Okwelogu, Emmanuel; Raftis, Jennifer B; Bruce, Lorraine; Poland, Craig A; Duffin, Rodger; Fokkens, Paul H B; Boere, A John F; Leseman, Daan L A C; Megson, Ian L; Whitfield, Phil D; Ziegler, Kerstin; Tammireddy, Seshu; Hadjidemetriou, Marilena; Bussy, Cyrill; Cassee, Flemming R; Newby, David E; Kostarelos, Kostas; Miller, Mark R Nature Nanotechnology; 19 (3): 271 - 272. 2024. 10.1038/s41565-023-01572-3.
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Graphene oxide activates canonical TGFβ signalling in a human chondrocyte cell line via increased plasma membrane tension
Ogene, Leona; Woods, Steven; Hetmanski, Joseph; Lozano, Neus; Karakasidi, Angeliki; Caswell, Patrick T; Kostarelos, Kostas; Domingos, Marco A N; Vranic, Sandra; Kimber, Susan J Nanoscale; 16 (11): 5653 - 5664. 2024. 10.1039/d3nr06033k.
2023
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Defect-free graphene enhances enzyme delivery to fibroblasts derived from patients with lysosomal storage disorders
Chen, YX; Taufiq, T; Zeng, NT; Lozano, N; Karakasidi, A; Church, H; Jovanovic, A; Jones, SA; Panigrahi, A; Larrosa, I; Kostarelos, K; Casiraghi, C; Vranic, S Nanoscale; 15 (21): 9348 - 9364. 2023. 10.1039/d2nr04971f. IF: 6.700
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Delivery of graphene oxide nanosheets modulates glutamate release and normalizes amygdala synaptic plasticity to improve anxiety-related behavior
Pati, E; Biagioni, AF; Casani, R; Lozano, N; Kostarelos, K; Cellot, G; Ballerini, L Nanoscale; 15 (46): 18581 - 18591. 2023. 10.1039/d3nr04490d. IF: 6.700
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Graphene oxide elicits microbiome-dependent type 2 immune responses via the aryl hydrocarbon receptor
Peng, GT; Sinkko, HM; Alenius, H; Lozano, N; Kostarelos, K; Bräutigam, L; Fadeel, B Nature Nanotechnology; 18 (1): 42 - +. 2023. 10.1038/s41565-022-01260-8. IF: 38.300
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Graphene Oxide Nanoscale Platform Enhances the Anti-Cancer Properties of Bortezomib in Glioblastoma Models
Sharp, PS; Stylianou, M; Arellano, LM; Neves, JC; Gravagnuolo, AM; Dodd, A; Barr, K; Lozano, N; Kisby, T; Kostarelos, K Advanced Healthcare Materials; 12 (3): e2201968. 2023. 10.1002/adhm.202201968. IF: 10.000
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Graphene Oxide Nanosheets Hamper Glutamate Mediated Excitotoxicity and Protect Neuronal Survival In An In vitro Stroke Model
Tortella, L; Santini, I; Lozano, N; Kostarelos, K; Cellot, G; Ballerini, L Chemistry-A European Journal; 29 (67): e202301762. 2023. 10.1002/chem.202301762. IF: 4.300
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Graphene Oxide Nanosheets Reduce Astrocyte Reactivity to Inflammation and Ameliorate Experimental Autoimmune Encephalomyelitis
Di Mauro, G; Amoriello, R; Lozano, N; Carnasciali, A; Guasti, D; Becucci, M; Cellot, G; Kostarelos, K; Ballerini, C; Ballerini, L Acs Nano; 17 (3): 1965 - 1978. 2023. 10.1021/acsnano.2c06609. IF: 17.100
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Human lung organoids predict response to carbon-based nanomaterials and model pulmonary fibrosis
Issa, R; Lozano, N; Kostarelos, K; Vranic, S Tissue Engineering Part a; 29 (13-14) 2023. . IF: 4.100
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Lung Persistence, Biodegradation, and Elimination of Graphene-Based Materials are Predominantly Size-Dependent and Mediated by Alveolar Phagocytes
Loret, T; de Luna, LAV; Lucherelli, MA; Fordham, A; Lozano, N; Bianco, A; Kostarelos, K; Bussy, C Small; 19 (39): e2301201. 2023. 10.1002/smll.202301201. IF: 13.300
2022
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Graphene oxide modulates dendritic cell ability to promote T cell activation and cytokine production
Parker, H; Gravagnuolo, AM; Vranic, S; Crica, LE; Newman, L; Carnell, O; Bussy, C; Dookie, RS; Prestat, E; Haigh, SJ; Lozano, N; Kostarelos, K; MacDonald, AS Nanoscale; 14 (46): 17297 - 17314. 2022. 10.1039/d2nr02169b. IF: 8.307
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Innate but Not Adaptive Immunity Regulates Lung Recovery from Chronic Exposure to Graphene Oxide Nanosheets
Loret T., de Luna L.A.V., Fordham A., Arshad A., Barr K., Lozano N., Kostarelos K., Bussy C. Advanced Science; 9 (11, 2104559) 2022. 10.1002/advs.202104559. IF: 16.806
Graphene has drawn a lot of interest in the material community due to unique physicochemical properties. Owing to a high surface area to volume ratio and free oxygen groups, the oxidized derivative, graphene oxide (GO) has promising potential as a drug delivery system. Here, the lung tolerability of two distinct GO varying in lateral dimensions is investigated, to reveal the most suitable candidate platform for pulmonary drug delivery. Following repeated chronic pulmonary exposure of mice to GO sheet suspensions, the innate and adaptive immune responses are studied. An acute and transient influx of neutrophils and eosinophils in the alveolar space, together with the replacement of alveolar macrophages by interstitial ones and a significant activation toward anti-inflammatory subsets, are found for both GO materials. Micrometric GO give rise to persistent multinucleated macrophages and granulomas. However, neither adaptive immune response nor lung tissue remodeling are induced after exposure to micrometric GO. Concurrently, milder effects and faster tissue recovery, both associated to a faster clearance from the respiratory tract, are found for nanometric GO, suggesting a greater lung tolerability. Taken together, these results highlight the importance of dimensions in the design of biocompatible 2D materials for pulmonary drug delivery system. © 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.
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Lung recovery from DNA damage induced by graphene oxide is dependent on size, dose and inflammation profile
de Luna, LAV; Loret, T; Fordham, A; Arshad, A; Drummond, M; Dodd, A; Lozano, N; Kostarelos, K; Bussy, C Particle And Fibre Toxicology; 19 (1) 2022. 10.1186/s12989-022-00502-w. IF: 9.112
2021
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Graphene Oxide Nanosheets Interact and Interfere with SARS-CoV-2 Surface Proteins and Cell Receptors to Inhibit Infectivity
Unal M.A., Bayrakdar F., Nazir H., Besbinar O., Gurcan C., Lozano N., Arellano L.M., Yalcin S., Panatli O., Celik D., Alkaya D., Agan A., Fusco L., Suzuk Yildiz S., Delogu L.G., Akcali K.C., Kostarelos K., Yilmazer A. Small; 17 (25, 2101483) 2021. 10.1002/smll.202101483. IF: 13.281
Nanotechnology can offer a number of options against coronavirus disease 2019 (COVID-19) acting both extracellularly and intracellularly to the host cells. Here, the aim is to explore graphene oxide (GO), the most studied 2D nanomaterial in biomedical applications, as a nanoscale platform for interaction with SARS-CoV-2. Molecular docking analyses of GO sheets on interaction with three different structures: SARS-CoV-2 viral spike (open state – 6VYB or closed state – 6VXX), ACE2 (1R42), and the ACE2-bound spike complex (6M0J) are performed. GO shows high affinity for the surface of all three structures (6M0J, 6VYB and 6VXX). When binding affinities and involved bonding types are compared, GO interacts more strongly with the spike or ACE2, compared to 6M0J. Infection experiments using infectious viral particles from four different clades as classified by Global Initiative on Sharing all Influenza Data (GISAID), are performed for validation purposes. Thin, biological-grade GO nanoscale (few hundred nanometers in lateral dimension) sheets are able to significantly reduce copies for three different viral clades. This data has demonstrated that GO sheets have the capacity to interact with SARS-CoV-2 surface components and disrupt infectivity even in the presence of any mutations on the viral spike. GO nanosheets are proposed to be further explored as a nanoscale platform for development of antiviral strategies against COVID-19. © 2021 The Authors. Small published by Wiley-VCH GmbH
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Graphene oxide prevents lateral amygdala dysfunctional synaptic plasticity and reverts long lasting anxiety behavior in rats
Franceschi Biagioni A., Cellot G., Pati E., Lozano N., Ballesteros B., Casani R., Coimbra N.C., Kostarelos K., Ballerini L. Biomaterials; 271 (120749) 2021. 10.1016/j.biomaterials.2021.120749. IF: 12.479
Engineered small graphene oxide (s-GO) sheets were previously shown to reversibly down-regulate glutamatergic synapses in the hippocampus of juvenile rats, disclosing an unexpected translational potential of these nanomaterials to target selective synapses in vivo. Synapses are anatomical specializations acting in the Central Nervous System (CNS) as functional interfaces among neurons. Dynamic changes in synaptic function, named synaptic plasticity, are crucial to learning and memory. More recently, pathological mechanisms involving dysfunctional synaptic plasticity were implicated in several brain diseases, from dementia to anxiety disorders. Hyper-excitability of glutamatergic neurons in the lateral nucleus of the amygdala complex (LA) is substantially involved in the storage of aversive memory induced by stressful events enabling post-traumatic stress disorder (PTSD). Here we translated in PTSD animal model the ability of s-GO, when stereotaxically administered to hamper LA glutamatergic transmission and to prevent the behavioral response featured in long-term aversive memory. We propose that s-GO, by interference with glutamatergic plasticity, impair LA-dependent memory retrieval related to PTSD. © 2021 The Authors
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Shedding plasma membrane vesicles induced by graphene oxide nanoflakes in brain cultured astrocytes
Musto M., Parisse P., Pachetti M., Memo C., Di Mauro G., Ballesteros B., Lozano N., Kostarelos K., Casalis L., Ballerini L. Carbon; 176: 458 - 469. 2021. 10.1016/j.carbon.2021.01.142. IF: 9.594
Microvesicles (MVs) generated and released by astrocytes, the brain prevalent cells, crucially contribute to intercellular communication, representing key vectorized systems able to spread and actively transfer signaling molecules from astrocytes to neurons, ultimately modulating target cell functions. The increasing clinical relevance of these signaling systems requires a deeper understanding of MV features, currently limited by both their nanoscale dimensions and the low rate of their constituent release. Hence, to investigate the features of such glial signals, nanotechnology-based approaches and the applications of unconventional, cost-effective tools in generating MVs are needed. Here, small graphene oxide (s-GO) nanoflakes are used to boost MVs shedding from astrocytes in cultures and s-GO generated MVs are compared with those generated by a natural stimulant, namely ATP, by atomic force microscopy, light scattering, attenuated total reflection–fourier transform infra-red and ultraviolet resonance Raman spectroscopy. We also report the ability of both types of MVs, upon acute and transient exposure of patch clamped cultured neurons, to modulate basal synaptic transmission, inducing a stable increase in synaptic activity accompanied by changes in neuronal plasma membrane elastic features. © 2021 The Author(s)
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The impact of graphene oxide sheet lateral dimensions on their pharmacokinetic and tissue distribution profiles in mice
Jasim D.A., Newman L., Rodrigues A.F., Vacchi I.A., Lucherelli M.A., Lozano N., Ménard-Moyon C., Bianco A., Kostarelos K. Journal of Controlled Release; 338: 330 - 340. 2021. 10.1016/j.jconrel.2021.08.028. IF: 9.776
Although the use of graphene and 2-dimensional (2D) materials in biomedicine has been explored for over a decade now, there are still significant knowledge gaps regarding the fate of these materials upon interaction with living systems. Here, the pharmacokinetic profile of graphene oxide (GO) sheets of three different lateral dimensions was studied. The GO materials were functionalized with a PEGylated DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid), a radiometal chelating agent for radioisotope attachment for single photon emission computed tomography (SPECT/CT) imaging. Our results revealed that GO materials with three distinct size distributions, large (l-GO-DOTA), small (s-GO-DOTA) and ultra-small (us-GO-DOTA), were sequestered by the spleen and liver. Significant accumulation of the large material (l-GO-DOTA) in the lungs was also observed, unlike the other two materials. Interestingly, there was extensive urinary excretion of all three GO nanomaterials indicating that urinary excretion of these structures was not affected by lateral dimensions. Comparing with previous studies, we believe that the thickness of layered nanomaterials is the predominant factor that governs their excretion rather than lateral size. However, the rate of urinary excretion was affected by lateral size, with large GO excreting at slower rates. This study provides better understanding of 2D materials in vivo behaviour with varying structural features. © 2021
2020
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Intracerebral Injection of Graphene Oxide Nanosheets Mitigates Microglial Activation Without Inducing Acute Neurotoxicity: A Pilot Comparison to Other Nanomaterials
Portioli C., Bussy C., Mazza M., Lozano N., Jasim D.A., Prato M., Bianco A., Bentivoglio M., Kostarelos K. Small; 16 (48, 2004029) 2020. 10.1002/smll.202004029. IF: 11.459
Carbon-based nanomaterials (CNMs) are being explored for neurological applications. However, systematic in vivo studies investigating the effects of CNM nanocarriers in the brain and how brain cells respond to such nanomaterials are scarce. To address this, functionalized multiwalled carbon nanotubes and graphene oxide (GO) sheets are injected in mice brain and compared with charged liposomes. The induction of acute neuroinflammatory and neurotoxic effects locally and in brain structures distant from the injection site are assessed up to 1 week postadministration. While significant neuronal cell loss and sustained microglial cell activation are observed after injection of cationic liposomes, none of the tested CNMs induces either neurodegeneration or microglial activation. Among the candidate nanocarriers tested, GO sheets appear to elicit the least deleterious neuroinflammatory profile. At molecular level, GO induces moderate activation of proinflammatory markers compared to vehicle control. At histological level, brain response to GO is lower than after vehicle control injection, suggesting some capacity for GO to reduce the impact of stereotactic injection on brain. While these findings are encouraging and valuable in the selection and design of nanomaterial-based brain delivery systems, they warrant further investigations to better understand the mechanisms underlying GO immunomodulatory properties in brain. © 2020 Wiley-VCH GmbH
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Optical nanogap antennas as plasmonic biosensors for the detection of miRNA biomarkers
Portela A., Calvo-Lozano O., Estevez M., Medina Escuela A., Lechuga L.M. Journal of Materials Chemistry B; 8 (19): 4310 - 4317. 2020. 10.1039/d0tb00307g. IF: 5.344
Nanoplasmonic biosensors based on nanogap antenna structures usually demand complex and expensive fabrication processes in order to achieve a good performance and sensitive detection. We here report the fabrication of large-area nanoplasmonic sensor chips based on nanogap antennas by employing a customized, simple and low-cost colloidal lithography process. By precisely controlling the angle for tilted e-beam metal evaporation, an elliptical mask is produced, which defines the total length of the dipole antenna nanostructures while assuring that the plasmonic response is oriented in the same direction along the sensor chip. Large-area sensor chips of nanogap antennas formed by pairs of gold nanodisks separated by gaps with an average size of 11.6 ± 4.7 nm are obtained. The optical characterization of the nanogap antenna structures in an attenuated total reflection (ATR) configuration shows a bulk refractive index sensitivity of 422 nm per RIU, which is in agreement with FDTD numerical simulations. The biosensing potential of the cm2-sized nanostructured plasmonic sensor chips has been evaluated for the detection of miRNA-210, a relevant biomarker for lung cancer diagnosis, through a DNA/miRNA hybridization assay. A limit of detection (LOD) of 0.78 nM (5.1 ng mL-1) was achieved with no need of further amplification steps, demonstrating the high sensitivity of these plasmonic nanogap antennas for the direct and label-free detection of low molecular weight biomolecules such as miRNAs. © The Royal Society of Chemistry 2020.
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Splenic Capture and in Vivo Intracellular Biodegradation of Biological-Grade Graphene Oxide Sheets
Newman L., Jasim D.A., Prestat E., Lozano N., De Lazaro I., Nam Y., Assas B.M., Pennock J., Haigh S.J., Bussy C., Kostarelos K. ACS Nano; 14 (8): 10168 - 10186. 2020. 10.1021/acsnano.0c03438. IF: 14.588
Carbon nanomaterials, including 2D graphene-based materials, have shown promising applicability to drug delivery, tissue engineering, diagnostics, and various other biomedical areas. However, to exploit the benefits of these materials in some of the areas mentioned, it is necessary to understand their possible toxicological implications and long-term fate in vivo. We previously demonstrated that following intravenous administration, 2D graphene oxide (GO) nanosheets were largely excreted via the kidneys; however, a small but significant portion of the material was sequestered in the spleen. Herein, we interrogate the potential consequences of this accumulation and the fate of the spleen-residing GO over a period of nine months. We show that our thoroughly characterized GO materials are not associated with any detectable pathological consequences in the spleen. Using confocal Raman mapping of tissue sections, we determine the sub-organ biodistribution of GO at various time points after administration. The cells largely responsible for taking up the material are confirmed using immunohistochemistry coupled with Raman spectroscopy, and transmission electron microscopy (TEM). This combination of techniques identified cells of the splenic marginal zone as the main site of GO bioaccumulation. In addition, through analyses using both bright-field TEM coupled with electron diffraction and Raman spectroscopy, we reveal direct evidence of in vivo intracellular biodegradation of GO sheets with ultrastructural precision. This work offers critical information about biological processing and degradation of thin GO sheets by normal mammalian tissue, indicating that further development and exploitation of GO in biomedicine would be possible. Copyright © 2020 American Chemical Society.