Department of Biochemistry and Molecular Biology; Imaging College of Shanxi Medical University; Imaging Department of the Affiliated Da Yi Hospital of Shanxi Medical University , Shanxi Medical University , Taiyuan 030001 , China.
Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering , Peking University , Beijing 100871 , China.
ACS Nano. 2019 Dec 24;13(12):13843-13852. doi: 10.1021/acsnano.9b04303. Epub 2019 Nov 11.
Compared with photon-induced binary cancer therapy, such as photothermal therapy (PTT) and photodynamic therapy (PDT), boron neutron capture therapy (BNCT) emerges as an alternative noninvasive treatment strategy that could overcome the shallow penetration of light. One key factor in performing successful BNCT is to accumulate a sufficient amount of B-10 (>20 ppm) within tumor cells, which has been a long-standing challenge for small-molecule-based boron drugs. Boron nitride nanoparticles (BNNPs) are promising boron carriers due to their high boron content and good biocompatibility, as certain types of BNNPs can undergo rapid degradation under physiological conditions. To design an on-demand degradable boron carrier, BNNPs were coated by a phase-transitioned lysozyme (PTL) that protects BNNPs from hydrolysis during blood circulation and can be readily removed by vitamin C after neutron capture therapy. According to PET imaging, the coated BNNPs exhibited high tumor boron accumulation while maintaining a good tumor to nontumor ratio. Tail-vein injections of vitamin C were followed by neutron irradiation, and BNNPs were found to be rapidly cleared from major organs according to ICP-OES analysis. Compared with the control group, animals treated with BNCT showed suppression of tumor growth, while almost negligible side effect was observed. This strategy not only utilized the high boron content of BNNPs but also successfully performed an on-demand degradation of BNNPs to avoid the potential toxicity caused by the long-term accumulation of nanoparticles.
与光子诱导的二元癌症治疗（如光热治疗[PTT]和光动力治疗[PDT]）相比，硼中子俘获治疗（BNCT）作为一种非侵入性替代治疗策略脱颖而出，可克服光的浅层穿透。成功进行 BNCT 的一个关键因素是在肿瘤细胞内积累足够量的 B-10（>20ppm），这一直是小分子硼药物面临的长期挑战。由于具有高硼含量和良好的生物相容性，氮化硼纳米粒子（BNNPs）是很有前途的硼载体，因为某些类型的 BNNPs 在生理条件下可以迅速降解。为了设计按需降解的硼载体，将 BNNPs 用相变溶菌酶（PTL）进行包覆，该溶菌酶可在血液循环过程中保护 BNNPs 免受水解，并在中子俘获治疗后可被维生素 C 轻易去除。根据 PET 成像，包覆的 BNNPs 表现出高肿瘤硼积累，同时保持良好的肿瘤与非肿瘤比值。尾静脉注射维生素 C 后进行中子辐照，根据 ICP-OES 分析发现 BNNPs 从主要器官迅速清除。与对照组相比，接受 BNCT 治疗的动物表现出肿瘤生长抑制，而几乎观察不到明显的副作用。该策略不仅利用了 BNNPs 的高硼含量，而且还成功地按需降解了 BNNPs，以避免纳米粒子长期积累带来的潜在毒性。
