{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T04:47:18Z","timestamp":1793767638443,"version":"4.6.1"},"reference-count":75,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T00:00:00Z","timestamp":1761782400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["24-15-00498"],"award-info":[{"award-number":["24-15-00498"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Endometriosis is a common gynecological condition that affects fertility in many women of reproductive age worldwide. This multifaceted disease exhibits a pathogenesis characterized by hormonal and immune system dysregulations, alongside increased angiogenic activity within the peritoneum. The aberrant proliferation of endometrial tissue outside the uterus is associated with vascularization in ectopic endometriotic lesions. Consequently, RNA interference (RNAi)-based angiogenic therapies targeting the VEGFA gene present a promising strategy for the treatment of endometriosis. To ensure the efficacy of RNAi-based therapy, it is critical to develop carriers capable of precisely delivering small interfering RNA (siRNA) to target cells. Additionally, the instability of polyplexes in vivo must be regarded as a pivotal aspect influencing the success of non-viral delivery. In this study, we introduce ternary polyplexes comprising siRNA and a carrier derived from an arginine\u2013histidine-rich peptide, which is further coated with a glutamate\u2013histidine-rich polymer modified using an SDF-1 chemokine-derived ligand for targeting CXCR4-expressing cells. The physicochemical characteristics of the siRNA-polyplexes, along with cellular toxicity and GFP gene silencing efficacy, were assessed in vitro. The anti-angiogenic potential of anti-VEGFA siRNA-polyplexes was evaluated by measuring the size of endometrial lesions, conducting immunohistochemical staining, and analyzing VEGFA gene expression. For in vivo experiment, a rat model of endometriosis induced by subcutaneous auto-transplantation of uterine tissue was utilized. A significant reduction in the growth of endometriotic implants and silencing of VEGFA gene expression was observed when compared to the saline-treated control group. The results of this study strongly suggest that the developed ternary polyplexes have significant potential as an efficient tool for the development of anti-angiogenic RNAi-based therapies for endometriosis.<\/jats:p>","DOI":"10.3390\/ijms262110582","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T01:23:59Z","timestamp":1761873839000},"page":"10582","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Anti-Angiogenic RNAi-Based Treatment of Endometriosis in a Rat Model Using CXCR4-Targeted Peptide Nanoparticles"],"prefix":"10.3390","volume":"26","author":[{"given":"Anna","family":"Egorova","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Genetics and Gene Therapy, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, Mendeleevskaya Line 3, 199034 Saint-Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana","family":"Freund","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics and Gene Therapy, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, Mendeleevskaya Line 3, 199034 Saint-Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8698-7904","authenticated-orcid":false,"given":"Iuliia","family":"Krylova","sequence":"additional","affiliation":[{"name":"Department of Pathology, Pavlov First Saint-Petersburg State Medical University, L\u2019va Tolstogo Street 6-8, 197022 Saint-Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0450-2365","authenticated-orcid":false,"given":"Anastasia","family":"Kislova","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics and Gene Therapy, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, Mendeleevskaya Line 3, 199034 Saint-Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2487-2423","authenticated-orcid":false,"given":"Anton","family":"Kiselev","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics and Gene Therapy, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, Mendeleevskaya Line 3, 199034 Saint-Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1016\/j.fertnstert.2007.03.069","article-title":"Differences in characteristics among 1000 women with endometriosis based on extent of disease","volume":"89","author":"Sinaii","year":"2008","journal-title":"Fertil. 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