Boosting Antitumour Efficacy and Immunity by Boron Neutron Capture Therapy with Size-Controlled Nanoparticles

Boron neutron capture therapy (BNCT) is emerging cancer radiotherapy requiring ¹⁰ B sensitizer. Although boronophenylalanine (BPA)–BNCT is approved clinically in Japan, the low tumour selectivity and retentivity result in the long-time infusion of high doses. Based on our finding of the size-controllable mechanochemical synthesis of boron-10 carbide nanoparticles ( ¹⁰ B ₄ C NPs), the 50 nm size NPs grafted with poly(glycerol), ¹⁰B₄C(50)-PG, is found to show superior tumour selectivity and retentivity to enhance the eradication efficacy at much lower dosage (5 mg [ ¹⁰ B] / kg (mouse)). The dosage is further reduced by twice neutron irradiation or combination with an immune checkpoint inhibitor (ICI). Antitumour immunity is found to be boosted by ¹⁰B₄C(50)-PG–BNCT to induce abscopal effect to treat remote or metastatic tumours and long-term memory to prevent cancer recurrence. Additionally, minimal side effects and gradual NP excretion are observed for one year. The ¹⁰ B ₄ C(50)-PG is concluded to be a promising ¹⁰ B carrier for clinical application of BNCT due to the prominent antitumour efficacy and immune-activation with minimal toxicity.