Hyaluronic acid-decorated carborane-TAT conjugation nanomicelles: A potential boron agent with enhanced selectivity of tumor cellular uptake.
Hyaluronic acid-decorated carborane-TAT conjugation nanomicelles: A potential boron agent with enhanced selectivity of tumor cellular uptake.
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DOI：
10.1016/j.colsurfb.2021.111826
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发表时间：
2021-05
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影响因子：
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通讯作者：
Hao-yu Quan;L. Fan;Yushu Huang;Xiaoyan Xia;Yang He;ShiYuan Liu;Jiahui Yu
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作者：
Hao-yu Quan;L. Fan;Yushu Huang;Xiaoyan Xia;Yang He;ShiYuan Liu;Jiahui Yu
硼中子俘获治疗（BNCT）作为一种新型的放射治疗方法受到了广泛的关注。BNCT中遇到的主要问题是肿瘤细胞对硼剂的摄取不足。本研究合成了具有细胞穿透功能的TAT-邻碳硼烷。这种偶联可以自组装形成带正电荷的碳硼烷-TAT胶束，然后吸附带负电荷的透明质酸（HA），得到核壳结构的碳硼烷-TAT @HA胶束。Carborane-TAT@HA胶束通过增强的渗透性和保留（EPR）效应以及HA结合CD 44受体的能力在肿瘤组织处表现出大量的硼摄取。Carborane-TAT@HA在体循环期间被HA壳包裹以避免达特与正常细胞的非特异性摄取，而HA壳的肿瘤微环境响应性脱落可暴露Carborane-TAT以穿透细胞膜进入肿瘤细胞。实验证明，该载体增强了肿瘤细胞对硼药物的选择性摄取，显示出良好的药物释放潜力，能够满足BNCT的基本要求。
Boron neutron capture therapy (BNCT) has received widespread attention as a new type of radiation therapy. The main problem encountered in BNCT is insufficient tumor cellular uptake of boron agents. In this study, cell-penetrating peptide TAT-conjugated o-carborane was synthesized. The conjugation can self-assemble to form positively charged carborane-TAT micelles, and then adsorb negatively charged hyaluronic acid (HA) to give core-shell structured carborane-TAT@HA micelles. Carborane-TAT@HA micelles exhibits a large amount of boron uptake at the tumor tissue through the enhanced permeability and retention (EPR) effect and the ability of HA to bind to CD44 receptors. Carborane-TAT@HA was wrapped by the HA shell during systemic circulation to avoid non-specific uptake of TAT with normal cells, while tumor microenvironment-responsive shedding of HA shell could expose Carborane-TAT to penetrate the cell membrane into tumor cells. Experiments have proved the enhanced selectivity of tumor cellular uptake of the boron drug, displayed excellent drug delivery potential, and can meet the basic requirements of BNCT.