Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, 200062, PR China.
Department of Radiology, Changzheng Hospital, Naval Medical University, Shanghai, 200003, PR China.
Colloids Surf B Biointerfaces. 2021 Aug;204:111826. doi: 10.1016/j.colsurfb.2021.111826. Epub 2021 May 10.
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.
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关注。BNCT 中遇到的主要问题是硼试剂在肿瘤细胞中的摄取不足。本研究合成了穿膜肽 TAT 偶联的邻-carborane。该缀合物可以自组装形成带正电荷的 carborane-TAT 胶束，然后吸附带负电荷的透明质酸（HA），得到具有核壳结构的 carborane-TAT@HA 胶束。通过增强的通透性和保留（EPR）效应以及 HA 与 CD44 受体结合的能力，carborane-TAT@HA 胶束在肿瘤组织中摄取大量硼。carborane-TAT@HA 在全身循环过程中被 HA 壳包裹，以避免 TAT 与正常细胞的非特异性摄取，而肿瘤微环境响应性的 HA 壳脱落可以使 Carborane-TAT 暴露并穿透细胞膜进入肿瘤细胞。实验证明了硼药物对肿瘤细胞摄取的增强选择性，表现出优异的药物递送潜力，能够满足 BNCT 的基本要求。
