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

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).