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

Zaichun You; Hang Qian; Changzheng Wang; Binfeng He; Jiawei Yan; Chengde Mao; Guansong Wang

doi:10.1016/j.biomaterials.2015.07.015

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

Biomaterials. 2015 Oct:67:137-50. doi: 10.1016/j.biomaterials.2015.07.015. Epub 2015 Jul 16.

Authors

Zaichun You¹, Hang Qian², Changzheng Wang³, Binfeng He³, Jiawei Yan², Chengde Mao⁴, Guansong Wang⁵

Affiliations

¹ Institute of Respiratory Diseases, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China; Department of Emergency, Xinqiao Hospital, Chongqing 400037, China.
² State Key Lab of Physical Chemistry of Solid Surfaces, and Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.
³ Institute of Respiratory Diseases, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
⁴ Department of Chemistry, Purdue University, West Lafayette, IN 47907, USA. Electronic address: mao@purdue.edu.
⁵ Institute of Respiratory Diseases, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China. Electronic address: wanggs2003@hotmail.com.

PMID: 26210180
DOI: 10.1016/j.biomaterials.2015.07.015

Abstract

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.

Keywords: Anoxia; Autophagy; DNA nanostructures; DNA nanotubes; Self-assembly; mTOR; siRNA.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Autophagy* / drug effects
Cell Death / drug effects
Cell Hypoxia / drug effects
Cell Proliferation / drug effects
Cell Survival / drug effects
DNA / metabolism*
Endocytosis / drug effects
Flow Cytometry
Microtubule-Associated Proteins / metabolism
Muscle, Smooth, Vascular / cytology*
Myocytes, Smooth Muscle / cytology*
Myocytes, Smooth Muscle / ultrastructure
Nanotubes / chemistry*
Nanotubes / toxicity
Nanotubes / ultrastructure
Phagosomes / drug effects
Phagosomes / metabolism
Proliferating Cell Nuclear Antigen / metabolism
RNA, Small Interfering / metabolism*
Signal Transduction / drug effects
TOR Serine-Threonine Kinases / metabolism*
Transfection

Substances

Microtubule-Associated Proteins
Proliferating Cell Nuclear Antigen
RNA, Small Interfering
DNA
TOR Serine-Threonine Kinases