Receptor-mediated active targeting and tumor microenvironment responsive systems from polymeric micelles have been studied for rapid cellular internalization and triggered drug release. Previously we have constructed redox-responsive polymeric micelles composed of vitamin E succinate conjugated hyaluronic acid (HA-ss-TOS), which are able to actively target CD44 proteins and quickly release loaded drugs upon exposure to high levels of glutathione (GSH) in tumor cells. In the present study, we found that despite different cellular internalization mechanisms, micelles showed strong antineoplastic effects on 4T1 and B16F10 cells due to redox responsiveness. HA-ss-TOS-PTX micelles exhibited an excellent tumor targeting ability and prolonged retention time compared to Taxol in vivo. In addition, a superior antitumor effect was achieved compared to PTX-loaded insensitive micelles (HA-TOS-PTX) and Taxol. Our results revealed that PTX-loaded HA-ss-TOS micelles could enhance the antineoplastic efficacy of PTX for breast cancer and melanoma treatment and, thus, deserve further attention.

中文翻译：

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氧化还原敏感的透明质酸基纳米药物通过各种内在化机制对不同癌细胞的细胞毒性增强。

已经研究了来自聚合物微团的受体介导的主动靶向和肿瘤微环境响应系统，用于快速细胞内在化和触发药物释放。以前，我们已经构建了由维生素E琥珀酸酯共轭透明质酸（HA-ss-TOS）组成的氧化还原反应性聚合物胶束，该胶束能够主动靶向CD44蛋白，并在暴露于肿瘤中高水平的谷胱甘肽（GSH）后迅速释放负载的药物细胞。在本研究中，我们发现尽管细胞内在化机制不同，但由于氧化还原反应性，胶束对4T1和B16F10细胞显示出强大的抗肿瘤作用。与体内紫杉醇相比，HA-ss-TOS-PTX胶束具有出色的肿瘤靶向能力和延长的保留时间。此外，与载有PTX的不敏感胶束（HA-TOS-PTX）和紫杉醇相比，具有更好的抗肿瘤作用。我们的结果表明，载有PTX的HA-ss-TOS胶束可以增强PTX在乳腺癌和黑色素瘤治疗中的抗肿瘤功效，因此值得进一步关注。