Precise delivery of 10B at cellular resolution in vivo enhances boron neutron capture therapy effect

Abstract

Boron neutron capture therapy (BNCT) is a promising binary radiotherapy that uses the isotope ¹⁰B and thermal neutron irradiation to induce lethal nuclear reactions in tumor cells. However, the effectiveness of BNCT often relies on the precise match between ¹⁰B and thermal neutrons. In this study, we developed a boron delivery system, integrating boron nitride (¹⁰BN) nanoparticles with microneedle (MN) patches (referred to as BN-MN). At equivalent dosages, BN-MN was able to maintain an intratumoral boron concentration above 20 ppm for over two hours, effectively aligning with the neutron irradiation time window. BN-MN also demonstrated efficient penetration and uniform distribution throughout the entire tumor tissue, with a tumor-to-normal tissue ratio (T/N) of 42 and a tumor-to-blood ratio (T/B) of 150, significantly superior to clinical boron drugs. More importantly, BN-MN efficiently delivered boron into tumor tissues at a precise cellular resolution, achieving an intracellular boron concentration 6.8 times higher than that obtained by BPA-loaded microneedles (BPA-MN). In vivo experiments demonstrated that the BN-MN system effectively inhibited tumor growth under neutron irradiation, with minimal systemic side effects. In summary, BN-MN perfectly matched neutron irradiation in terms of sufficient concentration, optimal retention time, and uniform spatial distribution, thereby enhancing the therapeutic efficacy and safety of BNCT.