Novel promising boron agents for boron neutron capture therapy: Current status and outlook on the future

Boron Neutron Capture Therapy (BNCT) is an emerging binary radiation therapy that exhibits high precision and lethlity for tumor. Its clinical efficacy has been demonstrated in locally aggressive tumors (glioma, melanoma, osteosarcoma, etc.). One paramount aspect of BNCT is the utilization of boron drugs, which has garnered significant attention from researchers. Currently, the primary boron agents employed in BNCT are L-p-boronophenylalanine (L-10BPA) and Na210B12H11SH (BSH). The former has a low boron content and necessitates repeated administration, while the latter lacks tumor selectivity and induces undifferentiated damage. The advent of novel and promising boron agents provides an opportunity for BNCT to achieve the desired clinical outcomes. In this review, we primarily focus on the research status of various boron carriers over the past decade. These carriers can be categorized based on different design strategies, including cell membrane targeting (LATs, GLUTs, peptides, etc.), nuclear targeting (nucleic acid derivatives, DNA embedders), enhanced permeability and retention (EPR) effect (liposome, polymer, inorganic nanoparticles) and tumor affinity (porphyrins). We delve into the challenges and breakthroughs associated with the clinical translation of boron-containing compounds and offer suggestions for the research and development of novel boron carriers.