{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T20:27:31Z","timestamp":1768076851937,"version":"3.49.0"},"reference-count":37,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,3,30]],"date-time":"2022-03-30T00:00:00Z","timestamp":1648598400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Competitiveness Operational Programme 2014\u20102020, Priority Axis1\/Action 1.1.4","award":["115\/13.09.2016\/MySMIS:104362"],"award-info":[{"award-number":["115\/13.09.2016\/MySMIS:104362"]}]},{"DOI":"10.13039\/501100006595","name":"Unitatea Executiva Pentru Finantarea Invatamantului Superior a Cercetarii Dezvoltarii si Inovarii","doi-asserted-by":"publisher","award":["PN-III-P4-ID-PCCF-2016-0050"],"award-info":[{"award-number":["PN-III-P4-ID-PCCF-2016-0050"]}],"id":[{"id":"10.13039\/501100006595","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Calcific aortic valve disease (CAVD) is a progressive inflammatory disorder characterized by extracellular matrix remodeling and valvular interstitial cells (VIC) osteodifferentiation leading to valve leaflets calcification and impairment movement. Runx2, the master transcription factor involved in VIC osteodifferentiation, modulates the expression of other osteogenic molecules. Previously, we have demonstrated that the osteoblastic phenotypic shift of cultured VIC is impeded by Runx2 silencing using fullerene (C60)-polyethyleneimine (PEI)\/short hairpin (sh)RNA-Runx2 (shRunx2) polyplexes. Since the use of polyplexes for in vivo delivery is limited by their instability in the plasma and the non-specific tissue interactions, we designed and obtained targeted, lipid-enveloped polyplexes (lipopolyplexes) suitable for (1) systemic administration and (2) targeted delivery of shRunx2 to osteoblast-differentiated VIC (oVIC). Vascular cell adhesion molecule (VCAM)-1 expressed on the surface of oVIC was used as a target, and a peptide with high affinity for VCAM-1 was coupled to the surface of lipopolyplexes encapsulating C60-PEI\/shRunx2 (V-LPP\/shRunx2). We report here that V-LPP\/shRunx2 lipopolyplexes are cyto- and hemo-compatible and specifically taken up by oVIC. These lipopolyplexes are functional as they downregulate the Runx2 gene and protein expression, and their uptake leads to a significant decrease in the expression of osteogenic molecules (OSP, BSP, BMP-2). These results identify V-LPP\/shRunx2 as a new, appropriately directed vehicle that could be instrumental in developing novel strategies for blocking the progression of CAVD using a targeted nanomedicine approach.<\/jats:p>","DOI":"10.3390\/ijms23073824","type":"journal-article","created":{"date-parts":[[2022,3,30]],"date-time":"2022-03-30T21:22:14Z","timestamp":1648675334000},"page":"3824","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["VCAM-1 Targeted Lipopolyplexes as Vehicles for Efficient Delivery of shRNA-Runx2 to Osteoblast-Differentiated Valvular Interstitial Cells; Implications in Calcific Valve Disease Treatment"],"prefix":"10.3390","volume":"23","author":[{"given":"Geanina","family":"Voicu","sequence":"first","affiliation":[{"name":"\u201cMedical and Pharmaceutical Bionanotechnologies\u201d Laboratory, Institute of Cellular Biology and Pathology \u201cNicolae Simionescu\u201d of the Romanian Academy, 050568 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Rebleanu","sequence":"additional","affiliation":[{"name":"\u201cMedical and Pharmaceutical Bionanotechnologies\u201d Laboratory, Institute of Cellular Biology and Pathology \u201cNicolae Simionescu\u201d of the Romanian Academy, 050568 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4922-9124","authenticated-orcid":false,"given":"Cristina Ana","family":"Mocanu","sequence":"additional","affiliation":[{"name":"\u201cMedical and Pharmaceutical Bionanotechnologies\u201d Laboratory, Institute of Cellular Biology and Pathology \u201cNicolae Simionescu\u201d of the Romanian Academy, 050568 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriela","family":"Tanko","sequence":"additional","affiliation":[{"name":"\u201cPathophysiology and Pharmacology\u201d Department, Institute of Cellular Biology and Pathology \u201cNicolae Simionescu\u201d of the Romanian Academy, 050568 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ionel","family":"Droc","sequence":"additional","affiliation":[{"name":"Central Military Hospital \u201cDr. Carol Davila\u201d, Cardiovascular Surgery Clinic, 010825 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7563-1267","authenticated-orcid":false,"given":"Cristina Mariana","family":"Uritu","sequence":"additional","affiliation":[{"name":"Centre of Advanced Research in Bionanoconjugates and Biopolymers, \u201cPetru Poni\u201d Institute of Macromolecular Chemistry, 700487 Iasi, Romania"},{"name":"Advanced Centre for Research-Development in Experimental Medicine, Grigore T. Popa University of Medicine and Pharmacy of Iasi, 700115 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4021-982X","authenticated-orcid":false,"given":"Mariana","family":"Pinteala","sequence":"additional","affiliation":[{"name":"Centre of Advanced Research in Bionanoconjugates and Biopolymers, \u201cPetru Poni\u201d Institute of Macromolecular Chemistry, 700487 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8079-4191","authenticated-orcid":false,"given":"Ileana","family":"Manduteanu","sequence":"additional","affiliation":[{"name":"\u201cMedical and Pharmaceutical Bionanotechnologies\u201d Laboratory, Institute of Cellular Biology and Pathology \u201cNicolae Simionescu\u201d of the Romanian Academy, 050568 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maya","family":"Simionescu","sequence":"additional","affiliation":[{"name":"\u201cMedical and Pharmaceutical Bionanotechnologies\u201d Laboratory, Institute of Cellular Biology and Pathology \u201cNicolae Simionescu\u201d of the Romanian Academy, 050568 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5245-160X","authenticated-orcid":false,"given":"Manuela","family":"Calin","sequence":"additional","affiliation":[{"name":"\u201cMedical and Pharmaceutical Bionanotechnologies\u201d Laboratory, Institute of Cellular Biology and Pathology \u201cNicolae Simionescu\u201d of the Romanian Academy, 050568 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1016\/S0140-6736(06)69208-8","article-title":"Burden of Valvular Heart Diseases: A Population-Based Study","volume":"368","author":"Nkomo","year":"2006","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"16006","DOI":"10.1038\/nrdp.2016.6","article-title":"Calcific Aortic Stenosis","volume":"2","author":"Lindman","year":"2016","journal-title":"Nat. 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