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 -
