Although aptamers are well-known as cell-specific membrane biomarkers for tumor-targeted therapy, it is important to avoid their degradation by nucleases in vivo. In this study, we developed a MUC1 aptamer–doxorubicin nanoconjugate (APT-DOX) through an acid-labile linkage and embedded APT-DOX into a thermosensitive hydrogel for antitumor therapy. The hydrogels exhibit a sol–gel transition upon intratumoral injection, resulting in the protection and controlled release control of APT-DOX with the shielding of the gel network. Moreover, the released APT-DOX was prone to be enriched at the tumor cells due to specific intracellular transport by the overexpressing MUC1 protein; however, APT-DOX regained the free DOX form via the rupture of the linkage under tumor cells lysosome acidic conditions and achieved increased concentration in the nucleus for antitumor treatment.

中文翻译：

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注射型微孔水凝胶中MUC1适体引导的酸不稳定的纳米共轭物的微环境控制。

尽管适体是众所周知的用于肿瘤靶向治疗的细胞特异性膜生物标志物，但重要的是避免它们在体内被核酸酶降解。在这项研究中，我们通过酸不稳定键开发了MUC1适体-阿霉素纳米共轭物（APT-DOX），并将APT-DOX嵌入热敏水凝胶中以进行抗肿瘤治疗。水凝胶在肿瘤内注射后表现出溶胶-凝胶转变，从而通过屏蔽凝胶网络实现了APT-DOX的保护和控释控制。此外，由于过表达的MUC1蛋白的特异性细胞内转运，释放的APT-DOX易于在肿瘤细胞富集。然而，