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

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 (He-4 and Li-7) 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. Boron neutron capture therapy (BNCT) is a type of radiotherapy that induces cell damage through a localized nuclear reaction. Here the authors describe the design of a carborane-based covalent organic framework as a boron capsule loaded with immune adjuvants for concurrent BNCT and immunotherapy, promoting anti-tumour immune responses in preclinical cancer models.

Automated summary

Boron neutron capture therapy (BNCT) is a clinically approved radiotherapy that selectively deposits deadly particles within cancer cells, but its abscopal anti-tumour effect has been limited. In this study, a boron capsule was engineered to synergize BNCT with controlled immune adjuvants release, promoting a potent anti-tumour immune response. The study revealed that the nuclear reaction in the boron capsule enhances drug release and uncovered the mechanism of BNCT-induced heat on anti-tumour immunity. In preclinical cancer models, BNCT and controlled drug release led to significant regression of both primary and distant tumour grafts.