Drug delivery efficiency often affects chemotherapy outcome due to dense collagen barrier in tumor environment. Here, we report a nanoparticle capable of pH and glutathione dual-responsive drug delivery to enhance the efficacy of breast cancer chemotherapy. Maleiminated polyethylene glycol and polylactide block copolymer were synthesized as a core material, doxorubicin was encapsulated into the nanoparticle by self-assembly. Thiocollagenase and maleimide were connected on the nanoparticle surface by click chemistry, and further coated with chondroitin sulfate as a protective layer to form dual-responsive doxorubicin nanoparticle. The results showed that the nanoparticle had the ability to penetrate deep tumor tissue, to target on CD44 of cancer cell, and to release doxorubicin in cancer cell in response to pH and glutathione signals, demonstrating superior anticancer efficacy in breast cancer-bearing mice. In conclusion, the dual-responsive nanoparticle could be used as a drug carrier to enhance drug delivery in breast cancer chemotherapy.

中文翻译：

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双响应纳米颗粒在乳腺癌化疗中增强药物递送


由于肿瘤环境中致密的胶原蛋白屏障，药物递送效率通常会影响化疗结果。在这里，我们报道了一种能够进行 pH 和谷胱甘肽双重反应药物递送的纳米颗粒，以增强乳腺癌化疗的疗效。以马来胺化聚乙二醇和聚丙交酯嵌段共聚物为核心材料，通过自组装将阿霉素封装到纳米颗粒中。通过点击化学将硫代胶原酶和马来酰亚胺连接在纳米颗粒表面，并进一步涂覆硫酸软骨素作为保护层，形成双响应的阿霉素纳米颗粒。结果表明，纳米颗粒具有穿透肿瘤深部组织的能力，靶向癌细胞的 CD44，并响应 pH 值和谷胱甘肽信号在癌细胞中释放阿霉素，在乳腺癌荷瘤小鼠中表现出优异的抗癌功效。总之，双响应纳米颗粒可用作药物载体，以增强乳腺癌化疗中的药物递送。