Microenvironmental Control of MUC1 Aptamer-Guided Acid-Labile Nanoconjugate within Injectable Microporous Hydrogels
Microenvironmental Control of MUC1 Aptamer-Guided Acid-Labile Nanoconjugate within Injectable Microporous Hydrogels
复制标题
可注射微孔水凝胶内 MUC1 适体引导的酸不稳定纳米缀合物的微环境控制
DOI：
10.1021/acs.bioconjchem.7b00324
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发表时间：
2017
影响因子：
4.7
通讯作者：
Qi Xiaole
中科院分区：
文献类型：
--
作者：
Xu Chenchen;Han Xiu;Jiang Yujie;Yuan Shengxiao;Wu Ziheng;Wu Zhenghong;Qi Xiaole
虽然适体是众所周知的肿瘤靶向治疗的细胞特异性膜生物标志物，但重要的是要避免它们在体内被核酸酶降解。在这项研究中，我们通过酸不稳定的链接开发了MUC1适配体-阿霉素纳米偶联物（APT-DOX），并将APT-DOX嵌入热敏水凝胶中用于抗肿瘤治疗。水凝胶在瘤内注射时表现出溶胶-凝胶转变，从而在凝胶网络的屏蔽下对APT-DOX产生保护和控释控制。此外，释放的APT-DOX容易因MUC1蛋白的过表达而在肿瘤细胞内特异性转运而富集；然而，在肿瘤细胞溶酶体酸性条件下，APT-DOX通过连锁断裂重新获得游离DOX形式，并在细胞核中达到更高的浓度，用于抗肿瘤治疗。
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.