Yiyao Liu1, Mengran Shi, Mingming Xu, Hong Yang, Chunhui Wu. 1. University of Electronic Science and Technology of China, School of Life Science and Technology, Department of Biophysics, Chengdu 610054, Sichuan, P.R. China. liuyiyao@hotmail.com
Abstract
OBJECTIVES: Technologies to increase tissue vascularity are critically important to the fields of tissue engineering and cardiovascular medicine. Angiogenic factors, like VEGF, have been widely investigated to induce vascular endothelial cell proliferation and angiogenesis for establishing a vascular network. However, effective transport of VEGF gene to target cells with minimal side effects remains a challenge despite the use of unique viral and non-viral delivery approaches. METHODS: This study presents a novel gene delivery system of fluorescein isothiocyanate (FITC) doped and poly(allylamine hydrochloride) (PAH) grafted Fe(3)O(4)@SiO(2) nanoparticles, which allows efficient loading of pVEGF to form Fe(3)O(4)@SiO(2)(FITC)/PAH/pVEGF nanocomplexes for VEGF gene delivery and cellular imaging. RESULTS: The nanocomplexes maintain their superparamagnetic property in the silica composites at room temperature, reaching a saturation magnetization value of 5.19 emu/g of material, and no appreciable change in magnetism even after PAH modification. The quantitative analysis of cellular internalization into the living human umbilical vein endothelial cells (HUVECs) demonstrated that the Fe(3)O(4)@SiO(2)(FITC)/PAH/pVEGF nanocomplexes could be entirely internalized by HUVECs, and exhibit high VEGF gene expression and an innocuous toxic profile. The magnetic resonance (MR) images showed that the superparamagnetic iron oxide core of Fe(3)O(4)@SiO(2)(FITC)/PAH/pVEGF nanocomplexes could also act as a contrast agent for MR imaging. This property provides a benefit for monitoring gene delivery. CONCLUSION: These data highlight multifunctional Fe(3)O(4)@SiO(2)(FITC)/PAH/pVEGF nanocomplexes as an attractive platform for gene delivery of angiogenesis, and also making it a potential candidate of nanoprobes for cellular fluorescent imaging or MR imaging.
OBJECTIVES: Technologies to increase tissue vascularity are critically important to the fields of tissue engineering and cardiovascular medicine. Angiogenic factors, like VEGF, have been widely investigated to induce vascular endothelial cell proliferation and angiogenesis for establishing a vascular network. However, effective transport of VEGF gene to target cells with minimal side effects remains a challenge despite the use of unique viral and non-viral delivery approaches. METHODS: This study presents a novel gene delivery system of fluorescein isothiocyanate (FITC) doped and poly(allylamine hydrochloride) (PAH) grafted Fe(3)O(4)@SiO(2) nanoparticles, which allows efficient loading of pVEGF to form Fe(3)O(4)@SiO(2)(FITC)/PAH/pVEGF nanocomplexes for VEGF gene delivery and cellular imaging. RESULTS: The nanocomplexes maintain their superparamagnetic property in the silica composites at room temperature, reaching a saturation magnetization value of 5.19 emu/g of material, and no appreciable change in magnetism even after PAH modification. The quantitative analysis of cellular internalization into the living human umbilical vein endothelial cells (HUVECs) demonstrated that the Fe(3)O(4)@SiO(2)(FITC)/PAH/pVEGF nanocomplexes could be entirely internalized by HUVECs, and exhibit high VEGF gene expression and an innocuous toxic profile. The magnetic resonance (MR) images showed that the superparamagnetic iron oxide core of Fe(3)O(4)@SiO(2)(FITC)/PAH/pVEGF nanocomplexes could also act as a contrast agent for MR imaging. This property provides a benefit for monitoring gene delivery. CONCLUSION: These data highlight multifunctional Fe(3)O(4)@SiO(2)(FITC)/PAH/pVEGF nanocomplexes as an attractive platform for gene delivery of angiogenesis, and also making it a potential candidate of nanoprobes for cellular fluorescent imaging or MR imaging.