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

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-...