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首页> 外文期刊>RSC Advances >A dual pH- and reduction-responsive anticancer drug delivery system based on PEG–SS–poly(amino acid) block copolymer
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A dual pH- and reduction-responsive anticancer drug delivery system based on PEG–SS–poly(amino acid) block copolymer

机译：基于PEG-SS-聚氨基酸嵌段共聚物的pH和还原反应双重抗癌药物递送系统

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摘要

A pH- and reduction-responsive anticancer drug delivery system was prepared and the triggerable and controllable drug release in response to stimuli was observed. In the first step, methoxy-poly(ethylene glycol) (mPEG) was conjugated with polysuccinimide (PSI) via disulfide linkages, and the PSI segment thereafter, was aminolyzed by 2-diisopropylaminoethylamine (DIPEA) and hydrazine hydrate (Hy). The obtained amphiphilic copolymer could form a bond with the model drug doxorubicin (DOX) at pH 7.4 via acid-labile hydrazone bonds, and more free DOX molecules could be encapsulated via hydrophobic interactions and π–π stacking between the aromatic rings, leading to DOX-loaded micelles formation. These polymers and polymeric micelles then were characterized. The results showed that the polymeric micelles exhibited dual pH- and reduction-responsive disassembly behaviors. Moreover, while the blank copolymers had excellent cytocompatibility, the DOX-loaded micelles showed an enhanced drug release profile and improved cytotoxicity with decrease of pH and/or the addition of glutathione (GSH). These results indicated that the novel nanoparticle based on PEG–SS–poly(amino acid) block copolymer is a promising candidate for a carrier in controllable anti-tumor drug delivery.
机译：制备了pH和还原反应的抗癌药物递送系统，并观察到了对刺激的可触发和可控制的药物释放。第一步，将甲氧基-聚（乙二醇）（mPEG）通过二硫键与聚琥珀酰亚胺（PSI）共轭，然后通过2-二异丙基氨基乙胺（DIPEA）和肼将PSI片段氨化水合物（Hy）。所获得的两亲共聚物可以通过酸不稳定的pH键在pH 7.4 下与模型药物阿霉素（DOX）形成键，并且可以通过疏水性将更多的自由DOX分子包裹起来芳环之间的相互作用和π-π堆积，导致形成DOX的胶束形成。然后表征这些聚合物和聚合物胶束。结果表明，聚合物胶束表现出双重的pH响应和还原响应分解行为。此外，尽管空白共聚物具有出色的细胞相容性，但随着pH值的降低和/或谷胱甘肽（GSH）的添加，载有DOX的胶束表现出增强的药物释放特性和改善的细胞毒性。这些结果表明，基于PEG-SS-聚（氨基酸）嵌段共聚物的新型纳米粒子是可控抗肿瘤药物输送载体的有希望的候选者。

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