Intracellular microenvironment responsive PEGylated polypeptide nanogels with ionizable cores for efficient doxorubicin loading and triggered release
Intracellular microenvironment responsive PEGylated polypeptide nanogels with ionizable cores for efficient doxorubicin loading and triggered release
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具有可电离核心的细胞内微环境响应性聚乙二醇化多肽纳米凝胶，可有效装载阿霉素并触发释放
DOI：
10.1039/c2jm32033a
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发表时间：
2012-01-01
影响因子：
--
通讯作者：
Chen, Xuesi
中科院分区：
文献类型：
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作者：
Shi, Fenghua;Ding, Jianxun;Chen, Xuesi
以氨基封端的聚乙二醇单甲氧基（mPEG-NH 2）为大分子引发剂，通过一步开环聚合法合成了两种二硫键交联的聚乙二醇-多肽共聚物。然后，将共聚物脱保护并分散在磷酸盐缓冲盐水中，产生PEG-多肽纳米凝胶。阿霉素（DOX），一个模型抗癌药物，有效地装载到纳米凝胶通过静电和疏水相互作用。在细胞内的还原性和酸性条件下，所有载药纳米凝胶的DOX释放都被加速，这是由Fickian扩散和纳米凝胶溶胀控制的。谷胱甘肽单酯（GSH-OEt）预处理的HeLa细胞中观察到细胞内DOX释放的增强。DOX负载纳米凝胶对GSH-OEt预处理的HeLa和HepG 2细胞的增殖抑制作用高于未预处理的细胞或丁硫醚亚砜（BSO）预处理的细胞。溶血试验表明纳米凝胶具有良好的血液相容性，纳米凝胶的存在可显著降低阿霉素的溶血率。这些特征表明，纳米凝胶可以有效地负载并递送DOX到肿瘤细胞中，并增强体外细胞增殖的抑制，为构建用于癌症治疗的有效药物递送系统提供了有利的平台。
Two kinds of reduction and pH responsive disulfide-cross-linked poly(ethylene glycol)-polypeptide copolymers were prepared through one-step ring-opening polymerization of gamma-benzyl-L-glutamate N-carboxyanhydride (BLG NCA) or epsilon-benzyloxycarbonyl-L-lysine N-carboxyanhydride (ZLL NCA) and L-cystine N-carboxyanhydride (LC NCA) with amino group terminated monomethoxy poly(ethylene glycol) (mPEG-NH2) as macroinitiator. Then, the copolymers were deprotected and dispersed in phosphate buffered saline, yielding PEG-polypeptide nanogels. Doxorubicin (DOX), a model anticancer drug, was effectively loaded into nanogels via electrostatic and hydrophobic interactions. The DOX release from all DOX-loaded nanogels was accelerated in intracellular reductive and acidic conditions, which controlled by Fickian diffusion and nanogels swelling. The enhanced intracellular DOX release was observed in glutathione monoester (GSH-OEt) pretreated HeLa cells. DOX-loaded nanogels showed higher cellular proliferation inhibition towards GSH-OEt pretreated HeLa and HepG2 cells than to unpretreated or buthionine sulfoximine (BSO) pretreated cells. Hemolysis tests indicated that nanogels were hemocompatible, and the presence of nanogels could reduce the hemolysis ratio (HR) of DOX significantly. These features suggest that the nanogels can efficiently load and deliver DOX into tumor cells and enhance the inhibition of cellular proliferation in vitro, providing a favorable platform to construct an efficient drug delivery system for cancer therapy.