Staff directory Markus Martincic

Markus Martincic

Postdoctoral Researcher
JDC-F 2018
Inorganic Nanoparticles



  • Neutron Activated 153Sm Sealed in Carbon Nanocapsules for in Vivo Imaging and Tumor Radiotherapy

    Wang J.T.-W., Klippstein R., Martincic M., Pach E., Feldman R., Šefl M., Michel Y., Asker D., Sosabowski J.K., Kalbac M., Da Ros T., Ménard-Moyon C., Bianco A., Kyriakou I., Emfietzoglou D., Saccavini J.-C., Ballesteros B., Al-Jamal K.T., Tobias G. ACS Nano; 14 (1): 129 - 141. 2020. 10.1021/acsnano.9b04898. IF: 14.588

    Radiation therapy along with chemotherapy and surgery remain the main cancer treatments. Radiotherapy can be applied to patients externally (external beam radiotherapy) or internally (brachytherapy and radioisotope therapy). Previously, nanoencapsulation of radioactive crystals within carbon nanotubes, followed by end-closing, resulted in the formation of nanocapsules that allowed ultrasensitive imaging in healthy mice. Herein we report on the preparation of nanocapsules initially sealing "cold" isotopically enriched samarium (152Sm), which can then be activated on demand to their "hot" radioactive form (153Sm) by neutron irradiation. The use of "cold" isotopes avoids the need for radioactive facilities during the preparation of the nanocapsules, reduces radiation exposure to personnel, prevents the generation of nuclear waste, and evades the time constraints imposed by the decay of radionuclides. A very high specific radioactivity is achieved by neutron irradiation (up to 11.37 GBq/mg), making the "hot" nanocapsules useful not only for in vivo imaging but also therapeutically effective against lung cancer metastases after intravenous injection. The high in vivo stability of the radioactive payload, selective toxicity to cancerous tissues, and the elegant preparation method offer a paradigm for application of nanomaterials in radiotherapy. Copyright © 2019 American Chemical Society.

  • Neutron-irradiated antibody-functionalised carbon nanocapsules for targeted cancer radiotherapy

    Wang J.T.-W., Spinato C., Klippstein R., Costa P.M., Martincic M., Pach E., Ruiz de Garibay A.P., Ménard-Moyon C., Feldman R., Michel Y., Šefl M., Kyriakou I., Emfietzoglou D., Saccavini J.-C., Ballesteros B., Tobias G., Bianco A., Al-Jamal K.T. Carbon; 162: 410 - 422. 2020. 10.1016/j.carbon.2020.02.060. IF: 8.821

    Radiotherapy is a cancer treatment utilising high doses of ionizing radiation to destroy cancer cells. Our team has pioneered neutron activation of 152Sm, filled and sealed into single-walled (SWCNTs) and multi-walled carbon nanotubes (MWCNTs), to create stable and high-dose radioactive carbon nanocapsules for cancer radiotherapy. In this work, MWCNTs filled with enriched 152SmCl3 (Sm@MWCNTs) were sealed and irradiated, followed by surface functionalisation with an epidermal growth factor receptor (EGFR)-targeting antibody. Characterisation of functionalised Sm@MWCNTs was carried out using thermogravimetric analysis, gel electrophoresis and transmission electron microscopy. The organ biodistribution of the radioactive functionalised 153Sm@MWCNTs and therapeutic efficacy were studied in an experimental melanoma lung metastatic tumour model in mice after intravenous injection. Quantitative biodistribution analyses showed high accumulation of 153Sm@MWCNT-Ab in lung. Significant tumour growth reduction was induced by both treatments of 153Sm@MWCNTs functionalised with or without the antibody after a single intravenous injection. Although EGFR targeting showed no improvement in therapeutic efficacy, reduced spleen toxicity and normal haematological profiles were obtained for both functionalised derivatives. The current study demonstrated the possibility of performing chemical functionalisation and antibody conjugation on radioactive nanocapsules post-irradiation for the preparation of targeted radiopharmaceuticals. © 2020 Elsevier Ltd


  • Non-cytotoxic carbon nanocapsules synthesized via one-pot filling and end-closing of multi-walled carbon nanotubes

    Martincic M., Vranic S., Pach E., Sandoval S., Ballesteros B., Kostarelos K., Tobias G. Carbon; 141: 782 - 793. 2019. 10.1016/j.carbon.2018.10.006. IF: 7.466

    Filled carbon nanotubes (CNTs) find application in a variety of fields that expand from sensors to supercapacitors going through targeted therapies. Bulk filling of CNTs in general results in samples that contain a large amount of non-encapsulated material external to the CNTs. The presence of external material can dominate the properties of the resulting hybrids and can also induce side effects when employed in the biomedical field. Unless the encapsulated payloads have a strong interaction with the inner CNT walls, an additional step is required to block the ends of the CNTs thus allowing the selective removal of the non-encapsulated compounds while preserving the inner cargo. Herein we present a fast, easy and versatile approach that allows both filling (NaI, KI, BaI2, GdCl3 and SmCl3) and end-closing of multi-walled CNTs in a single-step, forming “carbon nanocapsules”. Remarkably the encapsulation of GdCl3 and SmCl3 leads to the formation of tubular van der Waals heterostructures. The prepared nanocapsules are efficiently internalized by cells without inducing cytotoxicity, thus presenting a safe tool for the delivery of therapeutic and dianostic agents to cells. The synergies of novel carbon and inorganic hybrid materials can be explored using the present approach. © 2018 Elsevier Ltd


  • Epoxidation of carbon nanocapsules: Decoration of single-walled carbon nanotubes filled with metal halides

    D’Accolti L., Gajewska A., Kierkowicz M., Martincic M., Nacci A., Sandoval S., Ballesteros B., Tobias G., Da Ros T., Fusco C. Nanomaterials; 8 (3, 137) 2018. 10.3390/nano8030137. IF: 3.504

    Methyl(trifluoromethyl)dioxirane (TFDO) can be used for the oxyfunctionalization of SWCNTs filled with NaI and LuCl3 under mild conditions. The chosen metal halides are of interest for theranostics, both for imaging and therapy when in their radioactive form. The applied functionalization methodology does not require metal catalyst, preserves the integrity of the nanotubes during treatment, avoiding the release of the filling material. In this way, epoxidation can be considered as an efficient methodology for the functionalization of carbon nanocapsules, where the traditional harsh oxidation conditions by acids are not applicable. © 2018 2018 by the authors. Licensee MDPI, Basel, Switzerland.


  • Evaluation of the immunological profile of antibody-functionalized metal-filled single-walled carbon nanocapsules for targeted radiotherapy

    Perez Ruiz De Garibay A., Spinato C., Klippstein R., Bourgognon M., Martincic M., Pach E., Ballesteros B., Ménard-Moyon C., Al-Jamal K.T., Tobias G., Bianco A. Scientific Reports; 7 ( 42605) 2017. 10.1038/srep42605. IF: 4.259

    This study investigates the immune responses induced by metal-filled single-walled carbon nanotubes (SWCNT) under in vitro, ex vivo and in vivo settings. Either empty amino-functionalized CNTs [SWCNT-NH 2 (1)] or samarium chloride-filled amino-functionalized CNTs with [SmCl 3 @SWCNT-mAb (3)] or without [SmCl 3 @SWCNT-NH 2 (2)] Cetuximab functionalization were tested. Conjugates were added to RAW 264.7 or PBMC cells in a range of 1 μg/ml to 100 μg/ml for 24 h. Cell viability and IL-6/TNFα production were determined by flow cytometry and ELISA. Additionally, the effect of SWCNTs on the number of T lymphocytes, B lymphocytes and monocytes within the PBMC subpopulations was evaluated by immunostaining and flow cytometry. The effect on monocyte number in living mice was assessed after tail vein injection (150 μg of each conjugate per mouse) at 1, 7 and 13 days post-injection. Overall, our study showed that all the conjugates had no significant effect on cell viability of RAW 264.7 but conjugates 1 and 3 led to a slight increase in IL-6/TNFα. All the conjugates resulted in significant reduction in monocyte/macrophage cell numbers within PBMCs in a dose-dependent manner. Interestingly, monocyte depletion was not observed in vivo, suggesting their suitability for future testing in the field of targeted radiotherapy in mice. © The Author(s) 2017.


  • Carbon nanotubes allow capture of krypton, barium and lead for multichannel biological X-ray fluorescence imaging

    Serpell C.J., Rutte R.N., Geraki K., Pach E., Martincic M., Kierkowicz M., De Munari S., Wals K., Raj R., Ballesteros B., Tobias G., Anthony D.C., Davis B.G. Nature Communications; 7 ( 13118) 2016. 10.1038/ncomms13118. IF: 11.329

    The desire to study biology in situ has been aided by many imaging techniques. Among these, X-ray fluorescence (XRF) mapping permits observation of elemental distributions in a multichannel manner. However, XRF imaging is underused, in part, because of the difficulty in interpreting maps without an underlying cellular 'blueprint'; this could be supplied using contrast agents. Carbon nanotubes (CNTs) can be filled with a wide range of inorganic materials, and thus can be used as 'contrast agents' if biologically absent elements are encapsulated. Here we show that sealed single-walled CNTs filled with lead, barium and even krypton can be produced, and externally decorated with peptides to provide affinity for sub-cellular targets. The agents are able to highlight specific organelles in multiplexed XRF mapping, and are, in principle, a general and versatile tool for this, and other modes of biological imaging. © 2016 The Author(s).

  • Design of antibody-functionalized carbon nanotubes filled with radioactivable metals towards a targeted anticancer therapy

    Spinato C., Perez Ruiz De Garibay A., Kierkowicz M., Pach E., Martincic M., Klippstein R., Bourgognon M., Wang J.T.-W., Ménard-Moyon C., Al-Jamal K.T., Ballesteros B., Tobias G., Bianco A. Nanoscale; 8 (25): 12626 - 12638. 2016. 10.1039/c5nr07923c. IF: 7.760

    In the present work we have devised the synthesis of a novel promising carbon nanotube carrier for the targeted delivery of radioactivity, through a combination of endohedral and exohedral functionalization. Steam-purified single-walled carbon nanotubes (SWCNTs) have been initially filled with radioactive analogues (i.e. metal halides) and sealed by high temperature treatment, affording closed-ended CNTs with the filling material confined in the inner cavity. The external functionalization of these filled CNTs was then achieved by nitrene cycloaddition and followed by the derivatization with a monoclonal antibody (Cetuximab) targeting the epidermal growth factor receptor (EGFR), overexpressed by several cancer cells. The targeting efficiency of the so-obtained conjugate was evaluated by immunostaining with a secondary antibody and by incubation of the CNTs with EGFR positive cells (U87-EGFR+), followed by flow cytometry, confocal microscopy or elemental analyses. We demonstrated that our filled and functionalized CNTs can internalize more efficiently in EGFR positive cancer cells. © The Royal Society of Chemistry 2016.

  • Synthesis of dry SmCl3from Sm2O3revisited. Implications for the encapsulation of samarium compounds into carbon nanotubes

    Martincic M., Frontera C., Pach E., Ballesteros B., Tobias G. Polyhedron; 116: 116 - 121. 2016. 10.1016/j.poly.2016.03.045. IF: 2.108

    Samarium is a rare-earth metal with several applications in materials science. It is used in organic chemistry as a reducing agent and it is the active payload in samarium-153 lexidronam, a drug being used for palliative treatment of bone metastases. Recently, the encapsulation of samarium compounds into the cavities of carbon nanotubes has attracted interest for the development of the next generation of radiopharmaceuticals. In the present study, we explore different routes to afford the encapsulation of samarium based materials into single-walled carbon nanotubes. Anhydrous samarium(III) chloride, despite being highly hygroscopic, raises as an excellent candidate to achieve a high filling efficiency. We provide a protocol that allows the synthesis of anhydrous samarium(III) chloride starting from samarium(III) oxide in a fast and simple manner. Synchrotron X-ray powder diffraction confirmed the crystallinity and purity of the synthesized SmCl3. © 2016 Elsevier Ltd


  • Quantitative monitoring of the removal of non-encapsulated material external to filled carbon nanotube samples

    Martincic M., Pach E., Ballesteros B., Tobias G. Physical Chemistry Chemical Physics; 17 (47): 31662 - 31669. 2015. 10.1039/c5cp04664e. IF: 4.493

    The endohedral functionalization of carbon nanotubes with both organic and inorganic materials allows the development of tailored functional hybrids whose properties benefit from the synergistic effects of the constituent compounds. Bulk filling of carbon nanotubes (CNTs) results in samples that contain a large amount of non-encapsulated material external to the CNTs. The presence of the external material is detrimental to the processing and application of the resulting hybrids. Here we introduce the use of UV-Vis spectroscopy to monitor the cleaning process, i.e. the elimination of non-encapsulated compounds. Chrome azurol S has been employed to assess the bulk removal of external samarium(iii) chloride from filled single-walled carbon nanotubes. Chrome azurol S is of interest since it can be used to quantify a large variety of materials in a fast, accurate and reliable manner. The parameters that control the cleaning process have been optimized, including the time, temperature, volume and sonication, to achieve a fast and complete removal of the external material. © 2015 the Owner Societies.