{"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":1793767638905,"version":"4.6.1"},"reference-count":62,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,12,19]],"date-time":"2023-12-19T00:00:00Z","timestamp":1702944000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Russian Science Foundation","award":["19-15-00108II"],"award-info":[{"award-number":["19-15-00108II"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Endometriosis (EM) is a prevalent gynecological disease characterized by the abnormal growth of tissue similar to the endometrium outside of the uterus. This condition is accompanied by the development of new blood vessels in endometriotic lesions. While surgical intervention is effective in removing endometriotic lesions, some patients require multiple surgeries. Therefore, finding non-surgical treatments for EM is of great interest. One of the promising approaches is anti-angiogenic therapy using siRNA-therapeutics to target the expression of the VEGFA gene. Peptide-based polymers have shown promise as siRNA delivery systems due to their biocompatibility and ease of modification. We conducted a study to evaluate the effectiveness of the R6p-cRGD peptide carrier as a non-viral vehicle for delivering siRNA to endothelial cells in vitro and endometrial implants in vivo. We investigated the physicochemical properties of the siRNA-complexes, assessed cellular toxicity, and examined the efficiency of GFP and VEGFA genes silencing. Furthermore, we tested the anti-angiogenic effects of these complexes in cellular and animal models. The transfection with siRNA complexes led to a significant increase in VEGFA gene knockdown efficiency and a decrease in the migration of endothelial cells. For the animal model, we induced endometriosis in rats by transplanting endometrial tissue subcutaneously. We evaluated the efficiency of anti-angiogenic therapy for EM in vivo using anti-VEGF siRNA\/R6p-RGD complexes. During this assessment, we measured the volume of the implants, analyzed VEGFA gene expression, and conducted CD34 immunohistochemical staining. The results showed a significant decrease in the growth of endometriotic implants and in VEGFA gene expression. Overall, our findings demonstrate the potential of the R6p-cRGD peptide carrier as a delivery system for anti-angiogenic therapy of EM.<\/jats:p>","DOI":"10.3390\/ijms25010013","type":"journal-article","created":{"date-parts":[[2023,12,19]],"date-time":"2023-12-19T04:18:37Z","timestamp":1702959517000},"page":"13","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Polycondensed Peptide-Based Polymers for Targeted Delivery of Anti-Angiogenic siRNA to Treat Endometriosis"],"prefix":"10.3390","volume":"25","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":"Marianna","family":"Maretina","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"}]},{"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\/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":[[2023,12,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Lopes-Coelho, F., Martins, F., Pereira, S.A., and Serpa, J. (2021). Anti-Angiogenic Therapy: Current Challenges and Future Perspectives. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22073765"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/j.biopha.2018.12.022","article-title":"Therapeutic targeting of angiogenesis molecular pathways in angiogenesis-dependent diseases","volume":"110","author":"Fallah","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Nishida, S., Takashima, Y., Udagawa, R., Ibaraki, H., Seta, Y., and Ishihara, H. (2023). A Multifunctional Hybrid Nanocarrier for Non-Invasive siRNA Delivery to the Retina. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15020611"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2009","DOI":"10.1007\/s10238-023-01039-8","article-title":"Current status and future of anti-angiogenic drugs in lung cancer","volume":"23","author":"Yan","year":"2023","journal-title":"Clin. Exp. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2004975","DOI":"10.1002\/smll.202004975","article-title":"Nanomedicines for Endometriosis: Lessons Learned from Cancer Research","volume":"17","author":"Moses","year":"2021","journal-title":"Small"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1056\/NEJMra1810764","article-title":"Endometriosis","volume":"382","author":"Zondervan","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.fertnstert.2016.12.024","article-title":"Long-term medical management of endometriosis with dienogest and with a gonadotropin-releasing hormone agonist and add-back hormone therapy","volume":"107","author":"Bedaiwy","year":"2017","journal-title":"Fertil. Steril."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1177\/1933719110395406","article-title":"Effect of vascular endothelial growth factor inhibition on endometrial implant development in a murine model of endometriosis","volume":"18","author":"Ricci","year":"2011","journal-title":"Reprod. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1177\/1933719112452941","article-title":"The Efficacy of Bevacizumab, Sorafenib, and Retinoic Acid on Rat Endometriosis Model","volume":"20","author":"Ozer","year":"2013","journal-title":"Reprod. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1093\/humupd\/dms026","article-title":"Anti-angiogenic treatment strategies for the therapy of endometriosis","volume":"18","author":"Laschke","year":"2012","journal-title":"Hum. Reprod. Update"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"791686","DOI":"10.3389\/fsurg.2021.791686","article-title":"Antiangiogenic Therapy as a New Strategy in the Treatment of Endometriosis? The First Case Report","volume":"8","author":"Fruscalzo","year":"2021","journal-title":"Front. Surg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1016\/S0002-9440(10)64251-4","article-title":"Therapeutic Effect of Angiostatin Gene Transfer in a Murine Model of Endometriosis","volume":"161","author":"Dabrosin","year":"2002","journal-title":"Am. J. Pathol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1210\/en.2004-0765","article-title":"The vascular endothelial growth factor (VEGF)\/VEGF receptor 2 pathway is critical for blood vessel survival in corpora lutea of pregnancy in the rodent","volume":"146","author":"Pauli","year":"2005","journal-title":"Endocrinology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/0092-8674(85)90322-8","article-title":"Identification and isolation of a 140 kd cell surface glycoprotein with properties expected of a fibronectin receptor","volume":"40","author":"Pytela","year":"1985","journal-title":"Cell"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1083\/jcb.200910104","article-title":"Targeting of drugs and nanoparticles to tumors","volume":"188","author":"Ruoslahti","year":"2010","journal-title":"J. Cell Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.placenta.2021.12.015","article-title":"Human implantation: The complex interplay between endometrial receptivity, inflammation, and the microbiome","volume":"117","author":"Sehring","year":"2022","journal-title":"Placenta"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1093\/molehr\/gan019","article-title":"Antiangiogenic and vascular-disrupting agents in endometriosis: Pitfalls and promises","volume":"14","author":"Donnez","year":"2008","journal-title":"Mol. Hum. Reprod."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1093\/humupd\/4.5.736","article-title":"Angiogenesis: A new theory for endometriosis","volume":"4","author":"Healy","year":"1998","journal-title":"Hum. Reprod. Update"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1016\/S0015-0282(02)03347-2","article-title":"Alterations in expression of endometrial endothelial nitric oxide synthase and \u03b1 v\u03b2 3 integrin in women with endometriosis","volume":"78","author":"Khorram","year":"2002","journal-title":"Fertil. Steril."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"330","DOI":"10.2174\/1568026615666150812120755","article-title":"Peptide modules for overcoming barriers of nucleic acids transport to cells","volume":"16","author":"Egorova","year":"2015","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1038\/nrd1960","article-title":"Artificial viruses: A nanotechnological approach to gene delivery","volume":"5","author":"Mastrobattista","year":"2006","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1038\/s41587-023-01824-6","article-title":"Why gene therapies must go virus-free","volume":"41","author":"Sheridan","year":"2023","journal-title":"Nat. Biotechnol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2188","DOI":"10.1039\/C7BM00584A","article-title":"Peptides, polypeptides and peptide-polymer hybrids as nucleic acid carriers","volume":"5","author":"Ahmed","year":"2017","journal-title":"Biomater. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.jconrel.2011.01.030","article-title":"Glutathione-responsive nano-vehicles as a promising platform for targeted intracellular drug and gene delivery","volume":"152","author":"Cheng","year":"2011","journal-title":"J. Control. Release"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Egorova, A., Selutin, A., Maretina, M., Selkov, S., Baranov, V., and Kiselev, A. (2020). Characterization of iRGD-Ligand Modified Arginine-Histidine-Rich Peptides for Nucleic Acid Therapeutics Delivery to \u03b1v\u03b23 Integrin-Expressing Cancer Cells. Pharmaceuticals, 13.","DOI":"10.3390\/ph13100300"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Egorova, A., Shtykalova, S., Selutin, A., Shved, N., Maretina, M., Selkov, S., Baranov, V., and Kiselev, A. (2021). Development of iRGD-Modified Peptide Carriers for Suicide Gene Therapy of Uterine Leiomyoma. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13020202"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Egorova, A., Shtykalova, S., Maretina, M., Selutin, A., Shved, N., Deviatkin, D., Selkov, S., Baranov, V., and Kiselev, A. (2022). Polycondensed Peptide Carriers Modified with Cyclic RGD Ligand for Targeted Suicide Gene Delivery to Uterine Fibroid Cells. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031164"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Egorova, A., Selutin, A., Maretina, M., Selkov, S., and Kiselev, A. (2022). Peptide-Based Nanoparticles for \u03b1v\u03b23 Integrin-Targeted DNA Delivery to Cancer and Uterine Leiomyoma Cells. Molecules, 27.","DOI":"10.3390\/molecules27238363"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Egorova, A., Petrosyan, M., Maretina, M., Bazian, E., Krylova, I., Baranov, V., and Kiselev, A. (2023). iRGD-Targeted Peptide Nanoparticles for Anti-Angiogenic RNAi-Based Therapy of Endometriosis. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15082108"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1021\/bc000056i","article-title":"Low molecular weight disulfide cross-linking peptides as nonviral gene delivery carriers","volume":"11","author":"McKenzie","year":"2000","journal-title":"Bioconjug. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.jconrel.2004.09.018","article-title":"Influence of TAT-peptide polymerization on properties and transfection activity of TAT\/DNA polyplexes","volume":"102","author":"Bisht","year":"2005","journal-title":"J. Control. Release"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1146\/annurev.biophys.26.1.139","article-title":"Flexibility of RNA","volume":"26","author":"Hagerman","year":"1997","journal-title":"Annu. Rev. Biophys. Biomol. Struct."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"13348","DOI":"10.1021\/bi048950a","article-title":"Lipidic Carriers of siRNA: Differences in the Formulation, Cellular Uptake, and Delivery with Plasmid DNA","volume":"43","author":"Spagnou","year":"2004","journal-title":"Biochemistry"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"12474","DOI":"10.1021\/la802088y","article-title":"DNA release dynamics from reducible polyplexes by atomic force microscopy","volume":"24","author":"Wan","year":"2008","journal-title":"Langmuir"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1016\/j.ijpharm.2012.10.020","article-title":"Characterization of reducible peptide oligomers as carriers for gene delivery","volume":"441","author":"Kiselev","year":"2013","journal-title":"Int. J. Pharm."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/j.jconrel.2011.09.093","article-title":"Uptake mechanisms of non-viral gene delivery","volume":"158","author":"Xiang","year":"2012","journal-title":"J. Control. Release"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1124\/pr.58.1.8","article-title":"Uptake pathways and subsequent intracellular trafficking in nonviral gene delivery","volume":"58","author":"Khalil","year":"2006","journal-title":"Pharmacol. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/0005-2736(94)90038-8","article-title":"Effect of liposome size on the circulation time and intraorgan distribution of amphipathic poly(ethylene glycol)-containing liposomes","volume":"1190","author":"Litzinger","year":"1994","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.ijbiomac.2018.12.152","article-title":"Receptor-mediated delivery of therapeutic RNA by peptide functionalized curdlan nanoparticles","volume":"126","author":"Ganbold","year":"2019","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/s10585-007-9132-4","article-title":"CNTO 95, a fully human anti \u03b1v integrin antibody, inhibits cell signaling, migration, invasion, and spontaneous metastasis of human breast cancer cells","volume":"25","author":"Chen","year":"2008","journal-title":"Clin. Exp. Metastasis"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1111\/j.1742-4658.2008.06339.x","article-title":"Interaction and functional association of protein disulfide isomerase with \u03b1v\u03b23 integrin on endothelial cells","volume":"275","author":"Swiatkowska","year":"2008","journal-title":"FEBS J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3734","DOI":"10.1073\/pnas.80.12.3734","article-title":"Permanent cell line expressing human factor VIII-related antigen established by hybridization","volume":"80","author":"Edgell","year":"1983","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1002\/adfm.200700884","article-title":"Self-assembled Cationic Peptide Nanoparticles Capable of Inducing Efficient Gene Expression In Vitro","volume":"18","author":"Wiradharma","year":"2008","journal-title":"Adv. Funct. Mater."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3966","DOI":"10.1016\/j.febslet.2009.10.036","article-title":"Correlation of mRNA and protein in complex biological samples","volume":"583","author":"Maier","year":"2009","journal-title":"FEBS Lett."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.vph.2006.01.005","article-title":"Angiogenesis\u2014A new target for future therapy","volume":"44","author":"Pandya","year":"2006","journal-title":"Vascul. Pharmacol."},{"key":"ref_46","unstructured":"Reinhart-King, C.A. (2008). Methods in Enzymology, Academic Press."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.canlet.2006.06.007","article-title":"The structure of the vascular network of tumors","volume":"248","author":"Ribatti","year":"2007","journal-title":"Cancer Lett."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1038\/s41434-018-0042-7","article-title":"Anti-angiogenic treatment of endometriosis via anti-VEGFA siRNA delivery by means of peptide-based carrier in a rat subcutaneous model","volume":"25","author":"Egorova","year":"2018","journal-title":"Gene Ther."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1080\/03007995.2020.1744120","article-title":"Use of dienogest in endometriosis: A narrative literature review and expert commentary","volume":"36","author":"Murji","year":"2020","journal-title":"Curr. Med. Res. Opin."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1093\/molehr\/gap063","article-title":"Progestins inhibit expression of MMPs and of angiogenic factors in human ectopic endometrial lesions in a mouse model","volume":"15","author":"Sannecke","year":"2009","journal-title":"Mol. Hum. Reprod."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2851","DOI":"10.1093\/humrep\/deq241","article-title":"Effect of dienogest administration on angiogenesis and hemodynamics in a rat endometrial autograft model","volume":"25","author":"Katayama","year":"2010","journal-title":"Hum. Reprod."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1159\/000331642","article-title":"Effects of dienogest on surgically induced endometriosis in rats after repeated oral administration","volume":"72","author":"Fischer","year":"2011","journal-title":"Gynecol. Obstet. Investig."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1016\/j.biomaterials.2011.09.077","article-title":"Gene therapy of endometriosis introduced by polymeric micelles with glycolipid-like structure","volume":"33","author":"Zhao","year":"2012","journal-title":"Biomaterials"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Wang, N., Liu, B., Liang, L., Wu, Y., Xie, H., Huang, J., Guo, X., Tan, J., Zhan, X., and Liu, Y. (2014). Antiangiogenesis Therapy of Endometriosis Using PAMAM as a Gene Vector in a Noninvasive Animal Model. BioMed Res. Int., 2014.","DOI":"10.1155\/2014\/546479"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"175","DOI":"10.2147\/IJWH.S5633","article-title":"Dienogest in long-term treatment of endometriosis","volume":"3","author":"Schindler","year":"2011","journal-title":"Int. J. Women\u2019s Health"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"100199","DOI":"10.1016\/j.mtadv.2021.100199","article-title":"Combination of photothermal, prodrug and tumor cell camouflage technologies for triple-negative breast cancer treatment","volume":"13","author":"Zhang","year":"2022","journal-title":"Mater. Today Adv."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Egorova, A.A., Shtykalova, S.V., Maretina, M.A., Sokolov, D.I., Selkov, S.A., Baranov, V.S., and Kiselev, A.V. (2019). Synergistic Anti-Angiogenic Effects Using Peptide-Based Combinatorial Delivery of siRNAs Targeting VEGFA, VEGFR1, and Endoglin Genes. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11060261"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"11098","DOI":"10.1039\/D1CS00271F","article-title":"Cysteine protecting groups: Applications in peptide and protein science","volume":"50","author":"Spears","year":"2021","journal-title":"Chem. Soc. Rev."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Costantini, E., Aielli, L., Serra, F., De Dominicis, L., Falasca, K., Di Giovanni, P., and Reale, M. (2022). Evaluation of Cell Migration and Cytokines Expression Changes under the Radiofrequency Electromagnetic Field on Wound Healing In Vitro Model. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23042205"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/0003-2697(82)90530-9","article-title":"Ultrasensitive staining of nucleic acids with silver","volume":"126","author":"Beidler","year":"1982","journal-title":"Anal. Biochem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.acthis.2012.08.006","article-title":"Pigment epithelial-derived factor expression in endometriotic lesions in a rat model of endometriosis","volume":"115","author":"Fu","year":"2013","journal-title":"Acta Histochem."},{"key":"ref_62","first-page":"14","article-title":"Influence of progesterone analogs on endometrioid heterotopia in experimental model of endometriosis","volume":"81","author":"Petrosyan","year":"2018","journal-title":"Eksp. Klin. Farmakol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/1\/13\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:41:19Z","timestamp":1760132479000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/1\/13"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,19]]},"references-count":62,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["ijms25010013"],"URL":"https:\/\/doi.org\/10.3390\/ijms25010013","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,19]]}}}