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Application of Nitroimidazole–Carbobane-Modified Phenylalanine Derivatives as Dual-Target Boron Carriers in Boron Neutron Capture Therapy

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journal contribution
posted on 04.12.2019 by Ruixi Li, Juanjuan Zhang, Jingxuan Guo, Yue Xu, Kunyuan Duan, Jinrong Zheng, Hao Wan, Zhenwei Yuan, Haiyan Chen
Boron neutron capture therapy (BNCT) has received extensive attention as noninvasive cell-level oncotherapy for treating solid cancer tumors. However, boron-containing drugs such as l-boronophenylalanine (BPA) and sodium borocaptate 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 the 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.