| Autor: |
Egorova A; Department of Genomic Medicine, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, Mendeleevskaya Line 3, 199034 Saint-Petersburg, Russia., Petrosyan M; Pharmacology Group, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, Mendeleevskaya Line 3, 199034 Saint-Petersburg, Russia., Maretina M; Department of Genomic Medicine, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, Mendeleevskaya Line 3, 199034 Saint-Petersburg, Russia., Bazian E; Pharmacology Group, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, Mendeleevskaya Line 3, 199034 Saint-Petersburg, Russia., Krylova I; Department of Pathology, Pavlov First Saint-Petersburg State Medical University, L'va Tolstogo Street 6-8, 197022 Saint-Petersburg, Russia., Baranov V; Department of Genomic Medicine, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, Mendeleevskaya Line 3, 199034 Saint-Petersburg, Russia., Kiselev A; Department of Genomic Medicine, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, Mendeleevskaya Line 3, 199034 Saint-Petersburg, Russia. |
| Abstrakt: |
Anti-angiogenic RNAi-based therapy can be considered as a possible strategy for the treatment of endometriosis (EM), which is the most common gynecological disease. Targeted delivery of siRNA therapeutics is a prerequisite for successful treatment without adverse effects. Here we evaluated the RGD1-R6 peptide carrier as a non-viral vehicle for targeted siRNA delivery to endothelial cells in vitro and endometrial implants in vivo. The physicochemical properties of the siRNA complexes, cellular toxicity, and GFP and VEGFA gene silencing efficiency were studied, and anti-angiogenic effects were proved in cellular and animal models. The modification of siRNA complexes with iRGD ligand resulted in a two-fold increase in gene knockdown efficiency and three-fold decrease in endothelial cells' migration in vitro. Modeling of EM in rats with the autotransplantation of endometrial tissue subcutaneously was carried out. Efficiency of anti-angiogenic EM therapy in vivo by anti-VEGF siRNA/RGD1-R6 complexes was evaluated by the implants' volume measurement, CD34 immunohistochemical staining, and VEGFA gene expression analysis. We observed a two-fold decrease in endometriotic implants growth and a two-fold decrease in VEGFA gene expression in comparison with saline-treated implants. RNAi-mediated therapeutic effects were comparable with Dienogest treatment efficiency in a rat EM model. Taken together, these findings demonstrate the advantages of RGD1-R6 peptide carrier as a delivery system for RNAi-based therapy of EM. |
