Qi Lingling, Liu Chao, Zhang Yingying, Zhang Zheao, Duan Hongxia, Zhao Heming, Xin Xin, Chen Liqing, Jin Mingji, Guan Youyan, Gao Zhonggao, Huang Wei
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Pharmaceutics, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Department of Urology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Pharmaceutics. 2021 Oct 25;13(11):1776. doi: 10.3390/pharmaceutics13111776.
Micelle is mainly used for drug delivery and is prepared from amphiphilic block copolymers. It can be formed into an obvious core-shell structure that can incorporate liposoluble drugs. However, micelles are not suitable for the encapsulation of water-soluble drugs, and it is also difficult to maintain stability in the systemic circulation. To solve these problems, a type of polymer material, Fmoc-Lys-PEG and Fmoc-Lys-PEG-RGD, was designed and synthesized. These copolymers could self-assemble into micelles driven by π-π stacking and the hydrophobic interaction of 9-fluorenylmethoxycarbony (Fmoc) and, at the same time, form a framework for a hydrogen-bonding environment in the core. Mitomycin C (MMC), as a water-soluble drug, can be encapsulated into micelles by hydrogen-bonding interactions. The interaction force between MMC and the polymers was analyzed by molecular docking simulation and Fourier transform infrared (FTIR). It was concluded that the optimal binding conformation can be obtained, and that the main force between the MMC and polymers is hydrogen bonding. Different types of MMC nanoparticles (NPs) were prepared and the physicochemical properties of them were systematically evaluated. The pharmacodynamics of the MMC NPs in vitro and in vivo were also studied. The results show that MMC NPs had a high uptake efficiency, could promote cell apoptosis, and had a strong inhibitory effect on cell proliferation. More importantly, the as-prepared NPs could effectively induce tumor cell apoptosis and inhibit tumor growth and metastasis in vivo.
胶束主要用于药物递送，由两亲性嵌段共聚物制备而成。它可以形成明显的核壳结构，能够包载脂溶性药物。然而，胶束不适用于包载水溶性药物，并且在体循环中也难以保持稳定性。为了解决这些问题，设计并合成了一种聚合物材料，即芴甲氧羰基-赖氨酸-聚乙二醇（Fmoc-Lys-PEG）和芴甲氧羰基-赖氨酸-聚乙二醇-整合素靶向肽（Fmoc-Lys-PEG-RGD）。这些共聚物可在芴甲氧羰基（Fmoc）的π-π堆积和疏水相互作用驱动下自组装成胶束，同时在核心形成氢键环境框架。丝裂霉素C（MMC）作为一种水溶性药物，可通过氢键相互作用被包载到胶束中。通过分子对接模拟和傅里叶变换红外光谱（FTIR）分析了MMC与聚合物之间的相互作用力。得出可以获得最佳结合构象，且MMC与聚合物之间的主要作用力为氢键的结论。制备了不同类型的MMC纳米颗粒（NPs），并对其理化性质进行了系统评估。还研究了MMC NPs在体外和体内的药效学。结果表明，MMC NPs具有较高的摄取效率，可促进细胞凋亡，对细胞增殖有较强的抑制作用。更重要的是，所制备的NPs在体内可有效诱导肿瘤细胞凋亡，抑制肿瘤生长和转移。
