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International Journal Of Bilogical Sciences

.: Home > International Journal Of Bilogical Sciences > 2014 > Volume 10 Number 2 > Ting Li, Guo-dong Wang, Yu-zhen Tan, Hai-jie Wang 

Inhibition of Lymphangiogenesis of Endothelial Progenitor Cells with VEGFR-3 siRNA Delivered with PEI-alginate Nanoparticles

Ting Li, Guo-dong Wang, Yu-zhen Tan, Hai-jie Wang 
Department of Anatomy, Histology and Embryology, Shanghai Medical School of Fudan University, Shanghai 200032, China  Corresponding author: Hai-jie Wang Professor, MD., PhD., Department of Anatomy, Histology and Embryology, Shanghai Medical School of Fudan University, 277# 138 Yixueyuan Road, Shanghai 200032, People’s Republic of China. Tel: +86-21-54237430; Fax: +86-21-54237430; E-mail:
Abstract :

Lymphangiogenesis is implicated in lymphatic metastasis of tumor cells. Recently, growing evidences show that endothelial progenitor cells (EPCs) are involved in lymphangiogenesis. This study has investigated effects of VEGF-C/VEGFR-3 (vascular endothelial growth factor receptor-3) signaling pathway on EPC differentiation and effectiveness of inhibiting lymphatic formation of EPCs with VEGFR-3 siRNA delivered in PEI (polyethylenimine)-alginate nanoparticles. CD34+ VEGFR-3+ EPCs were sorted from mononuclear cells of human cord blood. Under induction with VEGF-C, the cells differentiated toward lymphatic endothelial cells. The nanoparticles were formulated with 25 kDa branched PEI and alginate. The size and surface charge of PEI-alginate nanoparticles loading VEGFR-3 siRNA (N/P = 16) are 139.1 nm and 7.56 mV respectively. VEGFR-3 siRNA specifically inhibited expression of VEGFR-3 mRNA in the cells. After treatment with PEI-alginate/siRNA nanocomplexes, EPCs could not differentiate into lymphatic endothelial cells, and proliferation, migration and lymphatic formation of EPC-derived cells were suppressed significantly. These results demonstrate that VEGFR-3 signaling plays an important role in differentiation of CD34+ VEGFR-3+ EPCs. VEGFR-3 siRNA delivered with PEI-alginate nanoparticles can effectively inhibit differentiation and lymphangiogenesis of EPCs. Inhibiting VEGFR-3 signaling with siRNA/nanocomplexes would be a potential therapy for suppression of tumor lymphangiogenesis and lymphatic metastasis

Keywords :
VEGFR-3, endothelial progenitor cells, nanoparticles, polyethyleneimine, alginate

Date Deposited : 02 Feb 2016 10:43

Last Modified : 02 Feb 2016 10:43

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Volume 10, Number 2, - 2014 , ISSN 1449-2288

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