Reduction-responsive methoxy poly(ethylene glycol)-block-poly(S-tert-butylmercapto-L-cysteine) copolymers (i.e., mPEG₁₁₃-b-PBMLC₄ and mPEG₁₁₃-b-PBMLC₉) were facilely synthesized through primary amino-initiated ring-opening polymerization (ROP) of disulfide-containing N-carboxyanhydride monomer. The reduction-responsive block copolymers were then investigated for intracellular delivery of antitumor drug after forming smart micelles in vitro and in vivo. The micelles were denoted as P4M and P9M, respectively. Doxorubicin (DOX) was selected as a model chemotherapeutic agent, which was loaded into micelles via hydrophobic interaction. The drug loading efficiency (DLE) were detected to be 55.4 and 61.7 wt % for P4M and P9M, respectively. The loaded micelles, referred as P4M/DOX and P9M/DOX, exhibited spherical morphologies with hydrodynamic radii of 92.3 ± 2.3 and 80.2 ± 2.8 nm, respectively. Compared to P4M/DOX, P9M/DOX with a smaller size exhibited upregulated cell endocytosis and higher cytotoxicity to human breast cancer MCF-7 cells. Furthermore, the loading micelles, especially P9M/DOX, demonstrated improved antitumor efficacy toward an MCF-7 breast tumor-bearing BALB/c nude mouse model compared with free doxorubicin hydrochloride (DOX·HCl). This was also confirmed by the histopathological and immunohistochemical results. The above results demonstrated that the facially prepared smart polypeptide micelles exhibited a potent prospect in intracellular drug delivery in vitro and in vivo.

中文翻译：

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还原反应性多肽胶束用于抗肿瘤剂的细胞内递送。

还原应答性的甲氧基聚（乙二醇） -嵌段-聚（小号-叔-butylmercapto基-L-半胱氨酸）共聚物（即，MPEG ₁₁₃ - b -PBMLC ₄和MPEG ₁₁₃ - b -PBMLC ₉）通过伯氨基被轻便合成含二硫化物的N-羧基酸酐单体的R-引发的开环聚合（ROP）。然后研究了还原反应性嵌段共聚物在体外和体内形成智能胶束后在细胞内递送抗肿瘤药物的能力。。胶束分别表示为P4M和P9M。选择阿霉素（DOX）作为模型化学治疗剂，其通过疏水相互作用被加载到胶束中。P4M和P9M的载药效率（DLE）分别为55.4和61.7 wt％。加载的胶束称为P4M / DOX和P9M / DOX，其球形形态的流体力学半径分别为92.3±2.3和80.2±2.8 nm。与P4M / DOX相比，较小的P9M / DOX表现出上调的细胞内吞作用，并且对人乳腺癌MCF-7细胞具有更高的细胞毒性。此外，与游离阿霉素盐酸盐（DOX·HCl）相比，负载微团，特别是P9M / DOX，对MCF-7乳腺荷瘤BALB / c裸鼠模型表现出更高的抗肿瘤功效。组织病理学和免疫组织化学结果也证实了这一点。上述结果表明，面部制备的智能多肽胶束在细胞内药物递送方面显示出有力的前景。体外和体内。