Maximizing nuclear capture and fission reactions: The innovative potential of boron delivery agents for neutron capture therapy in cancer treatment.

Neutron capture therapy (NCT) is a binary radiotherapeutic modality that relies on the nuclear capture and fission reactions of boron-10 for the selective destruction of cancer cells. Boron delivery agents (BDAs) are used to selectively deliver boron-10 to cancer cells, where it can be activated by neutron irradiation to produce highly cytotoxic alpha particles and recoiling lithium-7 nuclei that cause localized DNA damage and cell death. The development of BDAs for NCT has been an area of active research for several decades, with significant progress made in recent years. Polyhedral boranes, boronated porphyrins, boronated antibodies and peptides, and boronated lipids and nanoparticles are among the most promising BDAs for NCT, each with unique pharmacokinetic properties that make them suitable for specific applications. In addition to the development of novel BDAs, there has also been progress in the optimization of neutron sources and treatment planning strategies for NCT. Clinical trials and preclinical studies have demonstrated the safety and efficacy of NCT with BDAs for the treatment of various cancer types. The promising results of these studies suggest that NCT with BDAs could become an important tool in the fight against cancer. This review links specific boron delivery agent chemotypes to documented tumor-to-normal selectivity data, maps computational modeling approaches directly onto the specific BDA design challenges they have addressed, and summarizes clinical trial outcomes reported to date.