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

TY - JOUR

T1 - Neutron-irradiated antibody-functionalised carbon nanocapsules for targeted cancer radiotherapy

AU - Wang, Julie Tzu-Wen

AU - Spinato, Cinzia

AU - Klippstein, Rebecca

AU - Costa, Pedro Miguel

AU - Martincic, Markus

AU - Pach, Elzbieta

AU - Ruiz De Garibay, Aritz Perez

AU - Ménard-moyon, Cécilia

AU - Feldman, Robert

AU - Michel, Yves

AU - Šefl, Martin

AU - Kyriakou, Ioanna

AU - Emfietzoglou, Dimitris

AU - Saccavini, Jean-Claude

AU - Ballesteros, Belén

AU - Tobias, Gerard

AU - Bianco, Alberto

AU - Al-Jamal, Khuloud T.

PY - 2020/6

Y1 - 2020/6

N2 - 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.

AB - 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.

U2 - 10.1016/j.carbon.2020.02.060

DO - 10.1016/j.carbon.2020.02.060

M3 - Article

SN - 0008-6223

VL - 162

SP - 410

EP - 422

JO - CARBON

JF - CARBON

ER -