A styrene-maleic acid copolymer-based boron carrier for tumor-retentive boron delivery in boron neutron capture...

Boron neutron capture therapy (BNCT) requires sustained, high intratumoral concentrations of ¹⁰B with minimal normal tissue exposure. However, small-molecule agents such as sodium borocaptate (BSH) and p-boronophenylalanine (BPA) often exhibit insufficient tumor selectivity and retention. In this study, we designed a covalent conjugate of BSH with an amphiphilic styrene-maleic acid copolymer (SMA), termed BSH-SMA, as a polymer-based boron carrier for tumor-retentive boron delivery. The BSH-SMA conjugate was synthesized via a thioester linkage and evaluated for boron loading, hydrodynamic diameter, interaction with albumin under purified-protein conditions, and pH-responsive behavior. Biodistribution was measured in tumor-bearing mice. Thermal neutron irradiation was performed 12 h post-injection, corresponding to the peak tumor boron concentration. In vitro, BSH-SMA showed interaction with albumin under purified-protein conditions, as indicated by size-exclusion chromatography, and exhibited an acid-enhanced association, manifested by increased turbidity at tumor-relevant pH values. In vivo, the conjugate achieved tumor-preferential boron delivery with a high tumor-to-normal tissue ratio. Upon neutron irradiation, BSH-SMA significantly suppressed tumor growth compared with controls. Hematoxylin and eosin staining revealed no obvious histopathological changes in the liver or kidneys. These results support the potential of BSH-SMA as a polymeric boron carrier for tumor-selective boron delivery and BNCT under the present experimental conditions.