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Functionalized multi-walled carbon nanotubes (MWCNTs) containing radioactive salts are proposed as a potential system for radioactivity delivery. MWCNTs are loaded with isotopically enriched 152-samarium chloride (

Functionalized multi-walled carbon nanotubes (MWCNTs) containing radioactive salts are proposed as a potential system for radioactivity delivery. MWCNTs are loaded with isotopically enriched 152-samarium chloride (152SmCl3), the ends of the MWCNTs are sealed by high temperature treatment, and the encapsulated 152Sm is neutron activated to radioactive 153Sm. The external walls of the radioactive nanocapsules are functionalized through arylation reaction, to introduce hydrophilic chains and increase the water dispersibility of CNTs. The organ biodistribution profiles of the nanocapsules up to 24 h are assessed in naïve mice and different tumor models in vivo. By quantitative γ-counting, 153SmCl3@MWCNTs-NH2 exhibite high accumulation in organs without leakage of the internal radioactive material to the bloodstream. In the treated mice, highest uptake is detected in the lung followed by the liver and spleen. Presence of tumors in brain or lung does not increase percentage accumulation of 153SmCl3@MWCNTs-NH2 in the respective organs, suggesting the absence of the enhanced permeation and retention effect. This study presents a chemical functionalization protocol that is rapid (∼one hour) and can be applied to filled radioactive multi-walled carbon nanocapsules to improve their water dispersibility for systemic administration for their use in targeted radiotherapy., We thank Thomas Swan & Co. Ltd for supplying the Eli-carb® MWCNTs. This work was supported by European Union's Seventh Framework Programme FP7, Project “RADDEL” [grant number 290023], Worldwide Cancer Research [grant number 12-1054], Biotechnology and Biological Sciences Research Council [grant number BB/J008656/1], European Union HORIZON 2020 MSCA RISE 2016, Project Carbo-Immap [grant number 734381], “Severo Ochoa” Programme for Centres of Excellence in R&D [grant numbers SEV-2015-0496, SEV-2017-0706], and Generalitat de Catalunya 2017 [grant number SGR 327]., With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000917-S).

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., This work received funding from the European Union’s Seventh Framework Programme (FP7-ITN Marie-Curie Actions, RADDEL, 290023). PM Costa would like to acknowledge the funding from the Wellcome Trust (WT103913). KT A-J would like to acknowledge the funding from Worldwide Cancer Research, UK (12–1054). This work was partly supported by the Centre National de la Recherche Scientifique (CNRS), Agence Nationale de la Recherche (ANR) through the LabEx project Chemistry of Complex Systems (ANR-10-LABX-0026_CSC), and the International Center for Frontier Research in Chemistry (icFRC). ICMAB and ICN2 acknowledge financial support from the Spanish Ministry of Economy and Competitiveness, through the “Severo Ochoa” Programme for Centres of Excellence in R&D (SEV-2015-0496 and SEV-2017-0706). We thank Thomas Swan Co. Ltd. for supplying CNT Elicarb® samples. We wish to acknowledge Cathy Royer and Valérie Demais for TEM analyses at the Plateforme Imagerie in Vitro at the Center of Neurochemistry (Strasbourg, France).

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., This work received funding from the European Union’s Seventh Framework Programme (FP7-ITN Marie-Curie Actions, RADDEL, 290023). K.T.A.-J. acknowledges funding from Worldwide Cancer Research (12-1054), M.K. from MEYS (LTC18039), and G.T. from Agaur (2017 SGR 581). ICMAB and ICN2 acknowledge financial support from the Spanish Ministry of Economy and Competitiveness, through the “Severo Ochoa” Programme for Centres of Excellence in R&D (SEV-2015-0496 and SEV-2017-0706). This work was partly supported by the Centre National de la Recherche Scientifique (CNRS), by the Agence Nationale de la Recherche (ANR) through the LabEx project Chemistry of Complex Systems (ANR-10-LABX-0026_CSC), and by the International Center for Frontier Research in Chemistry (icFRC). We acknowledge support by MEYS CR and EU -ESIF in the frame of Operational Programme Research Development and Education - project Pro-NanoEnviCz (Project No. CZ.02.1.01/0.0/0.0/16_013/0001821). We thank Thomas Swan Co. Ltd. for supplying CNT Elicarb samples. We are grateful to S. Sandoval (ICMAB) and C. Ramos (IQS-ICMAB) for assessing the length and diameter distribution of CNTs.

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 (