Recent advances and challenges in boron neutron capture therapy for cancer treatment

Boron neutron capture therapy (BNCT) is an emerging precision radiotherapy that combines biochemical targeting with neutron-induced nuclear reactions. Leveraging the high-cross section reaction between 10B and thermal neutrons, BNCT generates localized high linear energy transfer radiation (α and 7Li particles) that selectively destroys tumor cells. Its primary clinical advantage lies in delivering a lethal dose to malignancies while maintaining an excellent safety profile through minimal normal-tissue uptake. Recently, the field has undergone a paradigm shift: neutron sources have transitioned from large-scale nuclear reactors to compact, hospital accelerator-based neutron sources, significantly lowering the barrier to global clinical implementation. Concurrently, third-generation boron agents have addressed traditional delivery limitations by focusing on superior tumor selectivity and theranostic potential. Following successful clinical applications in refractory tumors such as glioblastoma and head and neck cancers, BNCT has received its clinical approvals. This review provides an integrated overview of BNCT from the perspectives of physical principles, molecular evolution of boron delivery systems, nanomedicine-enabled targeting strategies, and emerging clinical translation. We also discuss emerging strategies, particularly the combination of BNCT with immunotherapy, to offer a forward-looking perspective on the continued evolution and clinical integration of this multidisciplinary field.