Priority Research Directions in Tumor-Targeted Boron Delivery for Boron Neutron Capture Therapy

The primary obstacle to the widespread clinical implementation of Boron Neutron Capture Therapy (BNCT) for malignant tumors is the lack of highly efficient tumor-targeted boron delivery agents. Clinically approved compounds – boronophenylalanine (BPA) and sodium borocaptate (BSH) – exhibit significant limitations, necessitating the development of novel boron pharmaceuticals. This review surveys current research directions in boron-containing drug development for BNCT, focusing on preclinical studies in laboratory animals. Three principal strategies are analyzed: targeted agents (antibody- or ligand-based constructs targeting tumor receptors: EGFR, VEGFR, etc.); natural and unnatural boronated amino acids; nanocarrier-based systems – boron-loaded nanoparticles and liposomes. Effective BNCT agents must demonstrate selective tumor accumulation, achieving intratumoral boron concentrations ≥20 μg/g cancer tissue during neutron irradiation while minimizing accumulation in healthy tissues. We critically evaluate the boron delivery efficacy, the prospects, and limitations of each approach. Current evidence indicates that metabolismdriven delivery systems, such as unnatural cyclic amino acids and transferrin conjugates, show the greatest therapeutic potential. Conversely, receptor-mediated agents (ligands/antibodies) have yet to demonstrate sufficient tumor boron accumulation for clinical BNCT efficacy.