Regulation of vascular smooth muscle cell autophagy by DNA nanotube-conjugated mTOR siRNA

• Published in: Biomaterials Vol. 67; pp. 137 - 150
• Main Authors: You, Zaichun, Qian, Hang, Wang, Changzheng, He, Binfeng, Yan, Jiawei, Mao, Chengde, Wang, Guansong
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.10.2015
• Subjects: Advanced Basic Science; anaerobic conditions; Anoxia; Autophagy; Autophagy - drug effects; Biomedical materials; Cell Death - drug effects; cell growth; Cell Hypoxia - drug effects; Cell Proliferation - drug effects; Cell Survival - drug effects; Control; Dentistry; Deoxyribonucleic acid; DNA; DNA - metabolism; DNA nanostructures; DNA nanotubes; Endocytosis - drug effects; Flow Cytometry; gene therapy; Mammals; Microtubule-Associated Proteins - metabolism; mTOR; Muscle, Smooth, Vascular - cytology; Muscles; myocytes; Myocytes, Smooth Muscle - cytology; Myocytes, Smooth Muscle - ultrastructure; Nanostructure; nanotubes; Nanotubes - chemistry; Nanotubes - toxicity; Nanotubes - ultrastructure; Phagosomes - drug effects; Phagosomes - metabolism; Proliferating Cell Nuclear Antigen - metabolism; RNA, Small Interfering - metabolism; Self assembly; Signal Transduction - drug effects; siRNA; small interfering RNA; smooth muscle; Surgical implants; TOR Serine-Threonine Kinases - metabolism; Transfection; Anoxia; PCNA; LC3B; T-mTOR; AFM; DNA nanotubes; siRNA; FACS; DNA nanostructures; MTT; p-mTOR; Autophagy; DMEM; Self-assembly; PAH; RT-PCR; FBS; mTOR; VSMC; CLSM; mTORC1; TEM; PASMC; pulmonary arterial smooth muscle cell; methyl thiazolyl tetrazolium; fluorescence-activated cell sorting; mammalian target of rapamycin; reverse transcription-polymerase chain reaction; confocal laser scan microscopy; transmission electron microscopy; pulmonary arterial hypertension; microtubule-associated protein-1 light chain 3B; atomic force microscopy; total mammalian target of rapamycin protein; mammalian target of rapamycin complexes 1; Dulbecco's Modified Eagle's Medium; proliferating cell nuclear antigen; fetal bovine serum; phosphorylated mammalian target of rapamycin protein; vascular smooth muscle cell
• ISSN: 0142-9612; 1878-5905; 1878-5905
• DOI: 10.1016/j.biomaterials.2015.07.015

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.