Localized nuclear reaction breaks boron drug capsules loaded with immune adjuvants for cancer immunotherapy

Shi, Yaxin and Guo, Zhibin and Fu, Qiang and Shen, Xinyuan and Zhang, Zhongming and Sun, Wenjia and Wang, Jinqiang and Sun, Junliang and Zhang, Zizhu and Liu, Tong and Gu, Zhen and Liu, Zhibo (2023) Localized nuclear reaction breaks boron drug capsules loaded with immune adjuvants for cancer immunotherapy. Nature Communications, 14 (1): 1884. ISSN 2041-1723

Abstract

Boron neutron capture therapy (BNCT) was clinically approved in 2020 and exhibits remarkable tumour rejection in preclinical and clinical studies. It is binary radiotherapy that may selectively deposit two deadly high-energy particles (4He and 7Li) within a cancer cell. As a radiotherapy induced by localized nuclear reaction, few studies have reported its abscopal anti-tumour effect, which has limited its further clinical applications. Here, we engineer a neutron-activated boron capsule that synergizes BNCT and controlled immune adjuvants release to provoke a potent anti-tumour immune response. This study demonstrates that boron neutron capture nuclear reaction forms considerable defects in boron capsule that augments the drug release. The following single-cell sequencing unveils the fact and mechanism that BNCT heats anti-tumour immunity. In female mice tumour models, BNCT and the controlled drug release triggered by localized nuclear reaction causes nearly complete regression of both primary and distant tumour grafts.