title: Inhibition of lymphangiogenesis of endothelial progenitor cells with VEGFR-3 siRNA delivered with PEI-alginate nanoparticles.
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.
authors: Department of Anatomy, Histology and Embryology, Shanghai Medical School of Fudan University, Shanghai 200032, China.
authors: Ting
authors: T
authors: Li
authors: Department of Anatomy, Histology and Embryology, Shanghai Medical School of Fudan University, Shanghai 200032, China.
authors: Guo-dong
authors: GD
authors: Wang
authors: Department of Anatomy, Histology and Embryology, Shanghai Medical School of Fudan University, Shanghai 200032, China.
authors: Yu-zhen
authors: YZ
authors: Tan
authors: Department of Anatomy, Histology and Embryology, Shanghai Medical School of Fudan University, Shanghai 200032, China.
authors: Hai-jie
authors: HJ
authors: Wang
mesh_terms: D000464:Alginates; D018952:Antigens, CD34 / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement; D042783:Endothelial Cells / Q000166:cytology / Q000648:ultrastructure; D005312:Fetal Blood / Q000166:cytology; D020723:Glucuronic Acid; D006603:Hexuronic Acids; D006801:Humans; D042583:Lymphangiogenesis / Q000235:genetics*; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles; D011094:Polyethyleneimine; D034622:RNA Interference; D034741:RNA, Small Interfering; D013234:Stem Cells / Q000166:cytology / Q000648:ultrastructure; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D000464:Alginates; D018952:Antigens, CD34; D006603:Hexuronic Acids; D034741:RNA, Small Interfering; D020723:Glucuronic Acid; D011094:Polyethyleneimine; D040321:Vascular Endothelial Growth Factor Receptor-3
keywords: VEGFR-3; alginate.; endothelial progenitor cells; nanoparticles; polyethyleneimine