Application of nitroimidazole-carbobane-modified phenylalanine derivatives as dual-target boron carriers in boron neutron capture therapy.

Abstract

Boron neutron capture therapy (BNCT) has received extensive attention as non-invasive cell-level oncotherapy for treating solid cancer tumors. However, boron-containing drugs such as L-boronophenylalanine (BPA) and sodium borocaptate (BSH) have low boron content and/or poor tumor-targeting ability, limiting their application. In this study, we designed and synthesized a series of nontoxic, dual-target boron carriers (B139, B142, and B151) with the ability to accumulate specifically in tumor cells. We found that B139 uptake into hypoxic tumor regions was high, with a 70-fold boron content compared to BPA. In addition, in vivo observation showed that B139 can be trapped in tumor cells for a prolonged period and maintains an effective therapeutic concentration, with a peak boron concentration of 50.7 μg/g and a high tumor: blood boron ratio of >3, achieving ideal BNCT conditions. Cytotoxicity evaluation in mice further proved that B139 is safe and reliable. Therefore, B139 has great potential for BNCT application as a dual-target, safe, and efficient boron carrier.