Synergistic Anti-Angiogenic Effects Using Peptide-Based Combinatorial Delivery of siRNAs Targeting VEGFA, VEGFR1, and Endoglin Genes

Pharmaceutics

卷:11

AntonV. Kiselev¹  MariannaA. Maretina¹  VladislavS. Baranov¹  DmitryI. Sokolov¹  AnnaA. Egorova¹  SergeiA. Selkov¹  SofiaV. Shtykalova² 

[1] D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, 199034 Saint-Petersburg, Russia;

[2] Department of Genetics and Biotechnology, Saint-Petersburg State University, 199034 Saint-Petersburg, Russia;

关键词: VEGFA;    VEGFR1;    endoglin;    siRNA delivery;    peptide;    angiogenesis;    gene silencing;    migration;    proliferation;    endothelial cells;   

DOI  :  10.3390/pharmaceutics11060261

来源: DOAJ

【 摘 要 】

Angiogenesis is a process of new blood vessel formation, which plays a significant role in carcinogenesis and the development of diseases associated with pathological neovascularization. An important role in the regulation of angiogenesis belongs to several key pathways such as VEGF-pathways, TGF-β-pathways, and some others. Introduction of small interfering RNA (siRNA) against genes of pro-angogenic factors is a promising strategy for the therapeutic suppression of angiogenesis. These siRNA molecules need to be specifically delivered into endothelial cells, and non-viral carriers modified with cellular receptor ligands can be proposed as perspective delivery systems for anti-angiogenic therapy purposes. Here we used modular peptide carrier L1, containing a ligand for the CXCR4 receptor, for the delivery of siRNAs targeting expression of VEGFA, VEGFR1 and endoglin genes. Transfection properties of siRNA/L1 polyplexes were studied in CXCR4-positive breast cancer cells MDA-MB-231 and endothelial cells EA.Hy926. We have demonstrated the efficient down-regulation of endothelial cells migration and proliferation by anti-VEGFA, anti-VEGFR1, and anti-endoglin siRNA-induced silencing. It was found that the efficiency of anti-angiogenic treatment can be synergistically improved via the combinatorial delivery of anti-VEGFA and anti-VEGFR1 siRNAs. Thus, this approach can be useful for the development of therapeutic angiogenesis inhibition.

【 授权许可】

Unknown