mp9b00898_si_001.pdf (2.7 MB)
Application of Nitroimidazole–Carbobane-Modified Phenylalanine Derivatives as Dual-Target Boron Carriers in Boron Neutron Capture Therapy
journal contribution
posted on 2019-12-04, 13:03 authored by Ruixi Li, Juanjuan Zhang, Jingxuan Guo, Yue Xu, Kunyuan Duan, Jinrong Zheng, Hao Wan, Zhenwei Yuan, Haiyan ChenBoron 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.