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Open AccessArticle

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

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
*
Author to whom correspondence should be addressed.
Pharmaceutics 2019, 11(6), 261; https://doi.org/10.3390/pharmaceutics11060261
Received: 26 April 2019 / Revised: 30 May 2019 / Accepted: 3 June 2019 / Published: 6 June 2019
(This article belongs to the Special Issue Drug Delivery of siRNA Therapeutics)
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. View Full-Text
Keywords: VEGFA; VEGFR1; endoglin; siRNA delivery; peptide; angiogenesis; gene silencing; migration; proliferation; endothelial cells VEGFA; VEGFR1; endoglin; siRNA delivery; peptide; angiogenesis; gene silencing; migration; proliferation; endothelial cells
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MDPI and ACS Style

Egorova, A.A.; Shtykalova, S.V.; Maretina, M.A.; Sokolov, D.I.; Selkov, S.A.; Baranov, V.S.; Kiselev, A.V. Synergistic Anti-Angiogenic Effects Using Peptide-Based Combinatorial Delivery of siRNAs Targeting VEGFA, VEGFR1, and Endoglin Genes. Pharmaceutics 2019, 11, 261.

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