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

Yaxin Shi; Zhibin Guo; Qiang Fu; Xinyuan Shen; Zhongming Zhang; Wenjia Sun; Jinqiang Wang; Junliang Sun; Zizhu Zhang; Tong Liu; Zhen Gu; Zhibo Liu

doi:10.1038/s41467-023-37253-x

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

Nat Commun. 2023 Apr 5;14(1):1884. doi: 10.1038/s41467-023-37253-x.

Authors

Yaxin Shi^#¹, Zhibin Guo^#¹, Qiang Fu^#², Xinyuan Shen³, Zhongming Zhang⁴, Wenjia Sun⁵, Jinqiang Wang³, Junliang Sun⁵, Zizhu Zhang⁶, Tong Liu⁷, Zhen Gu^{8

9

10

11}, Zhibo Liu^{12

13

14

15}

Affiliations

¹ Beijing National Laboratory for Molecular Sciences, Radiochemistry and Radiation Chemistry Key Laboratory of Fundamental Science, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, China.
² The Centre of Nanoscale Science and Technology and Key Laboratory of Functional Polymer Materials, Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin, 300071, China.
³ Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
⁴ Engineering Department, Lancaster University, Lancaster, Lancashire, LA1 4YW, UK.
⁵ College of Chemistry and Molecular Engineering, Beijing National Laboratory for Molecular Sciences, Peking University, Beijing, 100871, China.
⁶ Beijing Nuclear Industry Hospital, Beijing, 100045, China.
⁷ Beijing Capture Tech Co. Ltd, Beijing, 102413, China.
⁸ Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China. guzhen@zju.edu.cn.
⁹ Jinhua Institute of Zhejiang University, Jinhua, 321299, China. guzhen@zju.edu.cn.
¹⁰ Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, China. guzhen@zju.edu.cn.
¹¹ Liangzhu Laboratory, Zhejiang University Medical Center, 311121, Hangzhou, China. guzhen@zju.edu.cn.
¹² Beijing National Laboratory for Molecular Sciences, Radiochemistry and Radiation Chemistry Key Laboratory of Fundamental Science, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, China. zbliu@pku.edu.cn.
¹³ Peking-Tsinghua Center for Life Sciences, Peking University, 100871, Beijing, China. zbliu@pku.edu.cn.
¹⁴ Changping Laboratory, 102206, Beijing, China. zbliu@pku.edu.cn.
¹⁵ Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, 100142, Beijing, China. zbliu@pku.edu.cn.

^# Contributed equally.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Boron / therapeutic use
Boron Compounds / therapeutic use
Boron Neutron Capture Therapy*
Female
Immunotherapy
Male
Mice
Neoplasms* / drug therapy
Neutrons

Substances

Boron
Boron Compounds