One-step preparation of reduction-responsive poly(ethylene glycol)-poly (amino acid)s nanogels as efficient intracellular drug delivery platforms
One-step preparation of reduction-responsive poly(ethylene glycol)-poly (amino acid)s nanogels as efficient intracellular drug delivery platforms
复制标题
一步制备还原响应聚乙二醇-聚氨基酸纳米凝胶作为有效的细胞内药物递送平台
DOI：
10.1039/c1py00360g
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发表时间：
2011-01-01
影响因子：
4.6
通讯作者：
Chen, Xuesi
中科院分区：
文献类型：
--
作者：
Ding, Jianxun;Shi, Fenghua;Chen, Xuesi
以端氨基聚乙二醇单甲醚（mPEG-NH 2）为大分子引发剂，通过L-苯丙氨酸N-羧酸酐（L-Phe NCA）和L-胱氨酸N-羧酸酐（L-Cys NCA）的一步开环聚合，合成了一系列二硫键交联的聚乙二醇-聚氨基酸星星共聚物。将聚乙二醇-聚氨基酸直接分散于pH 7.4的磷酸盐缓冲溶液中，制备了还原响应性聚乙二醇-聚氨基酸纳米凝胶。动态光散射（DLS）的测量结果表明，可还原的NG溶胀响应于10 mM谷胱甘肽（GSH）。阿霉素（DOX），蒽环类抗癌药物，装载到NG。体外释放实验结果表明，GSH浓度、聚氨基酸的含量和组成可调节其释放行为。细胞内DOX释放结果显示GSH预处理的亨里埃塔Lacks（HeLa）细胞内DOX释放增加。体外MTT法检测表明，NG具有良好的生物相容性，且对GSH预处理的HeLa细胞的增殖抑制作用强于未预处理的细胞。因此，NG可以有效地将抗癌药物递送到肿瘤细胞中并抑制细胞增殖，使得在癌症治疗中的有效化疗药物的靶向细胞内递送非常有希望。
A series of disulfide-core-cross-linked poly(ethylene glycol)-poly(amino acid)s star copolymers were synthesized through one-step ring-opening polymerization of L-phenylalanine N-carboxyanhydride (L-Phe NCA) and L-cystine N-carboxyanhydride (L-Cys NCA) with amino group terminated poly(ethylene glycol) monomethyl ether (mPEG-NH2) as macroinitiator. The reduction-responsive PEG-poly(amino acid)s nanogels (NGs) were prepared by directly dispersing the resultant PEG-poly(amino acid)s in phosphate buffer solution at pH 7.4. Dynamic light scattering (DLS) measurements showed that the reducible NG swelled in response to 10 mM glutathione (GSH). Doxorubicin (DOX), an anthracycline anticancer drug, was loaded into the NGs. The in vitro release results revealed that the release behaviors could be adjusted by GSH concentration, and poly(amino acid)s content and composition. The intracellular DOX release results showed that enhanced intracellular DOX release occurred in GSH pretreated Henrietta Lacks (HeLa) cells. In vitro methyl thiazolyl tetrazolium (MTT) assays indicated that the NGs were biocompatible, and DOX-loaded NG showed higher cellular proliferation inhibition towards GSH pretreated HeLa cells than that of non-pretreated cells. Therefore, the NGs can efficiently deliver anticancer drugs into tumor cells and inhibit cell proliferation, rendering highly promising for targeted intracellular delivery of operative chemotherapeutic drugs in cancer therapy.