One of the major challenges in anticancer therapy is the poor penetration of anticancer drugs into tumors, especially in solid tumors, resulting in decreased therapeutic efficacy in vivo. To solve some of these problems, in this study, a dual-responsive polymeric micellar system has been developed. This system exhibits an ultrasensitive response to the change of pH value from the extracellular environment to the intracellular environment, resulting in micellar swelling in cancer cells via the proton sponge effect. Moreover, once the swelled micelles escape from the lysosomes in cancer cells, the disulfide linkages are ruptured by GSH in the cytoplasm, leading to the rapid release of the encapsulated drugs into the cellular nuclei. The antitumor activity in pancreatic tumor-bearing mice reveals that this dual-responsive drug delivery system possesses a long blood circulation time and can significantly promote cell internalization and intracellular drug release, achieving a high anticancer efficacy with fewer side effects for normal tissues.

中文翻译：

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酸敏感和还原敏感的胶束可改善胰腺癌治疗的药物传递效率†

抗癌疗法中的主要挑战之一是抗癌药尤其是在实体瘤中难以渗透到肿瘤中，从而导致体内治疗效果下降。为了解决这些问题中的一些问题，在这项研究中，开发了一种双响应聚合物胶束系统。该系统对pH值从细胞外环境到细胞内环境的变化表现出超敏反应，从而导致癌细胞的胶束膨胀通过质子海绵效应。此外，一旦溶胀的胶束从癌细胞中的溶酶体中逸出，二硫键就会被细胞质中的GSH破坏，从而导致被包封的药物迅速释放到细胞核中。胰腺肿瘤小鼠的抗肿瘤活性表明，这种双重反应的药物递送系统具有较长的血液循环时间，并且可以显着促进细胞内在化和细胞内药物释放，从而实现了高抗癌功效，并且对正常组织的副作用更少。