Boronophenylalanine‐Functionalized Platinum Nanozymes Sensitizing Neutron Capture Therapy

Abstract Boron neutron capture therapy (BNCT), which uses high‐energy particles generated by the reaction of 10 B isotope with thermal neutrons to kill tumor cells precisely at the microscale, has become a promising treatment approach with aggressive and recurrent cancers. The development of highly selective boron drugs for tumor cells and devices with thermal neutron beams is crucial for BNCT. Borophenylalanine (BPA), the most widely used 10 B containing drug in clinic, has problems with fast metabolism and poor tumor retention. Therefore, to improve the therapeutic effect of BPA, this study reports highly 10 BPA‐loaded platinum nanoparticles (Pt‐ 10 BPA NPs) and conduct BNCT experiments with a neutron beam generated by an accelerator neutron source. The Pt‐ 10 BPA NPs achieve deep tumor penetration and retention, thereby significantly inhibiting the growth of subcutaneous colorectal tumors in mice. Furthermore, unlike classic drugs, the Pt‐ 10 BPA NPs have superior catalytic properties and can sensitize BNCT by increasing reactive oxygen species (ROS) production. Since the observation of improvements in immune responses induced by Pt‐ 10 BPA NPs sensitized BNCT, its further combination with immune checkpoint blockade therapy results in significant suppression of both primary and secondary tumors. In summary, this study provides a new aspect for the development of catalytic nanomedicines for BNCT sensitization.