We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Synergistic Anti-Angiogenic Effects Using Peptide-Based Combinatorial Delivery of siRNAs Targeting VEGFA, VEGFR1, and Endoglin Genes.
- Authors
Egorova, Anna A.; Shtykalova, Sofia V.; Maretina, Marianna A.; Sokolov, Dmitry I.; Selkov, Sergei A.; Baranov, Vladislav S.; Kiselev, Anton V.
- Abstract
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.
- Subjects
ENDOGLIN; SMALL interfering RNA; ENDOTHELIAL cells; CXCR4 receptors; CELL migration
- Publication
Pharmaceutics, 2019, Vol 11, Issue 6, p261
- ISSN
1999-4923
- Publication type
Article
- DOI
10.3390/pharmaceutics11060261