The antitumor activity of doxorubicin (DOX) is often limited owing to the occurrence of multidrug resistance (MDR) during treatment. Herein, we developed hybrid polymeric micelles, which consisted of pluronic F127 as long-circulating helper in blood, and phenylboronic ester-grafted pluronic P123 (PHE) as efflux and detoxification regulator to efficiently deliver DOX and reverse MDR in vivo. Hybrid F127/PHE micelles exhibited higher stability and drug encapsulation (~80%) than simple F127/P123 micelles due to its lower CMC, and displayed in vitro drug release in a hydrogen peroxide (H2O2)-sensitive manner. Besides, DOX-loaded hybrid micelles (F127/PHE-DOX) possessed higher cell-killing ability and induce more apoptotic in MDR-cells than other groups, which was probably because it not only could greatly increase intracellular drug concentration by inhibiting P-gp mediated drug efflux, but also promote reactive oxygen species (ROS) generation by decreasing glutathione (GSH) levels. Besides, in vivo evaluation indicated that F127/PHE-DOX could well accumulate at tumor regions and exhibit the strongest tumor growth inhibition (TGI 87.87%) accompanied with low side effects. As a result, F127/PHE micelles had great potentials as a platform for anticancer drugs delivery and tumor MDR reversal in clinical application.

中文翻译：

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具有抑制阿霉素外排和解毒作用的Pluronic胶束，可有效逆转乳腺癌的耐药性。

阿霉素（DOX）的抗肿瘤活性通常由于治疗期间发生多药耐药性（MDR）而受到限制。在本文中，我们开发了混合聚合物胶束，该胶束由作为血液中长效助剂的普朗尼克F127和接枝和解毒调节剂的苯基硼酸酯接枝的普朗尼克P123（PHE）组成，可有效地体内释放DOX和逆转MDR。杂合的F127 / PHE胶束由于其较低的CMC表现出比简单的F127 / P123胶束更高的稳定性和药物封装（〜80％），并以对过氧化氢（H2O2）敏感的方式显示了体外药物释放。此外，掺有DOX的杂交胶束（F127 / PHE-DOX）具有比其他组更高的细胞杀伤能力，并在MDR细胞中诱导更多的凋亡，这可能是因为它不仅可以通过抑制P-gp介导的药物外排而大大增加细胞内药物的浓度，还可以通过降低谷胱甘肽（GSH）的水平来促进活性氧（ROS）的产生。此外，体内评估表明F127 / PHE-DOX可以很好地积聚在肿瘤区域，并表现出最强的肿瘤生长抑制作用（TGI 87.87％），且副作用低。结果，F127 / PHE胶束在临床应用中具有作为抗癌药物传递和肿瘤MDR逆转的平台的巨大潜力。87％）伴有低副作用。因此，F127 / PHE胶束在临床应用中具有作为抗癌药物传递和肿瘤MDR逆转的平台的巨大潜力。87％）伴有低副作用。因此，F127 / PHE胶束在临床应用中具有作为抗癌药物传递和肿瘤MDR逆转的平台的巨大潜力。