Preferentially released miR-122 from cyclodextrin-based star copolymer nanoparticle enhances hepatoma chemotherapy by apoptosis induction and cytotoxics efflux inhibition.
Preferentially released miR-122 from cyclodextrin-based star copolymer nanoparticle enhances hepatoma chemotherapy by apoptosis induction and cytotoxics efflux inhibition.
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基于环糊精的星形共聚物纳米颗粒优先释放的 miR-122 通过诱导细胞凋亡和抑制细胞毒素外流增强肝癌化疗
DOI：
10.1016/j.bioactmat.2021.03.026
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发表时间：
2021-11
影响因子：
18.9
通讯作者：
Song T
中科院分区：
文献类型：
--
作者：
Xiong Q;Bai Y;Shi R;Wang J;Xu W;Zhang M;Song T
化疗作为癌症治疗中最常用的治疗方式之一，由于其低效的递送以及肝癌固有的化疗耐药性，对肝癌患者的益处有限。生物信息学分析鉴定了肝脏特异性microRNA-miR-122对于增强肝癌中的化学治疗功效的治疗作用。本文中，构建环糊精核星星共聚物纳米颗粒系统（sCDP/DOX/miR-122）以共递送miR-122与阿霉素（DOX）用于肝癌治疗。在该纳米系统中，miR-122通过sCDP的外阳离子聚（2-（二甲氨基）乙基甲基丙烯酸酯）链缩合，而DOX容纳在疏水性环糊精内腔中，从而赋予miR-122和DOX的顺序释放方式。优先释放的miR-122不仅通过下调Bcl-w和增强p53活性直接诱导细胞凋亡，而且通过抑制细胞毒性外排转运蛋白表达增加DOX积累，实现了对细胞抑制的协同性能。此外，与游离DOX和单独的sCDP/DOX相比，sCDP/DOX/miR-122显示出显著增加的体内抗肿瘤功效，表明其在肝癌治疗中的巨大前景。开发了基于环糊精的聚合物纳米颗粒以共递送miR-122和多柔比星。纳米颗粒依次将miR-122和多柔比星释放到HepG 2细胞中。优先释放的miR-122诱导细胞凋亡并抑制阿霉素流出。在体内实现了增强的抗肿瘤作用和降低的心脏毒性。
Chemotherapy, as one of the most commonly used treatment modalities for cancer therapy, provides limited benefits to hepatoma patients, owing to its inefficient delivery as well as the intrinsic chemo-resistance of hepatoma. Bioinformatic analysis identified the therapeutic role of a liver-specific microRNA — miR-122 for enhancing chemo-therapeutic efficacy in hepatoma. Herein, a cyclodextrin-cored star copolymer nanoparticle system (sCDP/DOX/miR-122) is constructed to co-deliver miR-122 with doxorubicin (DOX) for hepatoma therapy. In this nanosystem, miR-122 is condensed by the outer cationic poly (2-(dimethylamino) ethyl methacrylate) chains of sCDP while DOX is accommodated in the inner hydrophobic cyclodextrin cavities, endowing a sequential release manner of miR-122 and DOX. The preferentially released miR-122 not only directly induces cell apoptosis by down regulation of Bcl-w and enhanced p53 activity, but also increases DOX accumulation through inhibiting cytotoxic efflux transporter expression, which realizes synergistic performance on cell inhibition. Moreover, sCDP/DOX/miR-122 displays remarkably increased anti-tumor efficacy in vivo compared to free DOX and sCDP/DOX alone, indicating its great promising in hepatoma therapy. Cyclodextrin-based polymeric nanoparticle was developed to co-deliver miR-122 and doxorubicin. The nanoparticle sequentially released miR-122 and doxorubicin into HepG2 cells. The preferentially released miR-122 induces cell apoptosis and inhibits doxorubicin efflux. Enhanced anti-tumor effects with reduced cardiotoxicity were achieved in vivo.
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影响因子：
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