4.8 Article

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

Journal

CARBON
Volume 162, Issue -, Pages 410-422

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.carbon.2020.02.060

Keywords

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Funding

  1. European Union's Seventh Framework Programme (FP7-ITN Marie-Curie Actions, RADDEL) [290023]
  2. Wellcome Trust [WT103913]
  3. Worldwide Cancer Research, UK [12-1054]
  4. Centre National de la Recherche Scientifique (CNRS)
  5. Agence Nationale de la Recherche (ANR) through the LabEx project Chemistry of Complex Systems [ANR-10-LABX-0026_CSC]
  6. International Center for Frontier Research in Chemistry (icFRC)
  7. Spanish Ministry of Economy and Competitiveness, through the Severo Ochoa Programme for Centres of Excellence in RD [SEV-2015-0496, SEV-2017-0706]

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Radiotherapy is a cancer treatment utilising high doses of ionizing radiation to destroy cancer cells. Our team has pioneered neutron activation of Sm-152, filled and sealed into single-walled (SWCNT5) and multi-walled carbon nanotubes (MWCNT5), to create stable and high-dose radioactive carbon nanocapsules for cancer radiotherapy. In this work, MWCNT5 filled with enriched (SmCl3)-Sm-152 (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 Sm-153@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 Sm-153@MWCNT-Ab in lung. Significant tumour growth reduction was induced by both treatments of Sm-153@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 postirradiation for the preparation of targeted radiopharmaceuticals. (C) 2020 Elsevier Ltd. All rights reserved.

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