| Autor: |
Egorova AA; D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, 199034 Saint-Petersburg, Russia. egorova_anna@yahoo.com., Shtykalova SV; Department of Genetics and Biotechnology, Saint-Petersburg State University, 199034 Saint-Petersburg, Russia. sofia.shtykalova@gmail.com., Maretina MA; D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, 199034 Saint-Petersburg, Russia. marianna0204@gmail.com., Sokolov DI; D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, 199034 Saint-Petersburg, Russia. falcojugger@yandex.ru., Selkov SA; D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, 199034 Saint-Petersburg, Russia. selkovsa@mail.ru., Baranov VS; D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, 199034 Saint-Petersburg, Russia. baranov@vb2475.spb.edu.; Department of Genetics and Biotechnology, Saint-Petersburg State University, 199034 Saint-Petersburg, Russia. baranov@vb2475.spb.edu., Kiselev AV; D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, 199034 Saint-Petersburg, Russia. ankiselev@yahoo.co.uk. |
| Abstrakt: |
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. |
