Regulation of vascular smooth muscle cell autophagy by DNA nanotube-conjugated mTOR siRNA
Regulation of vascular smooth muscle cell autophagy by DNA nanotube-conjugated mTOR siRNA
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DNA纳米管缀合的mTOR siRNA对血管平滑肌细胞自噬的调节
DOI：
10.1016/j.biomaterials.2015.07.015
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发表时间：
2015
期刊：
影响因子：
14
通讯作者：
Wang Guansong
中科院分区：
文献类型：
--
作者：
You Zaichun;Qian Hang;Wang Changzheng;He Binfeng;Yan Jiawei;Mao Chengde;Wang Guansong
短干扰RNA（siRNA）的有效递送是基因治疗领域中的巨大挑战。在此，我们报告了一种基于程序化DNA自组装的哺乳动物雷帕霉素靶蛋白（mTOR）siRNA负载的DNA纳米管（DNA-NTs）递送纳米系统。我们证明这些siRNA-DNA-NTs可以通过内吞作用有效地转染到肺动脉平滑肌细胞（PASMCs）中;并且负载的mTOR siRNA在正常和缺氧条件下都可以诱导明显的自噬并抑制细胞生长。此外，我们发现mTOR siRNA可以控制PASMCs在缺氧条件下的自噬和增殖，这表明mTOR siRNA在PASMCs异常自噬的疾病中具有潜在的治疗应用。
The efficient delivery of short interfering RNA (siRNA) is an enormous challenge in the field of gene therapy. Herein, we report a delivery nanosystem based on programmed DNA self-assembly mammalian target of rapamycin (mTOR) siRNA-loaded DNA nanotubes (DNA-NTs). We demonstrate that these siRNA-DNA-NTs can be effectively transfected into pulmonary arterial smooth muscle cells (PASMCs) via endocytosis; and that the loaded mTOR siRNA can induce obvious autophagy and inhibit cell growth under both normal and hypoxic conditions. Moreover, we found that mTOR siRNA can control the autophagy and proliferation of PASMCs under hypoxic condition, suggesting a potential therapeutic application for mTOR siRNA in diseases involving abnormal autophagy in PASMCs.