دورية أكاديمية

Nanocarriers of shRNA-Runx2 directed to collagen IV as a nanotherapeutic system to target calcific aortic valve disease.

التفاصيل البيبلوغرافية
العنوان: Nanocarriers of shRNA-Runx2 directed to collagen IV as a nanotherapeutic system to target calcific aortic valve disease.
المؤلفون: Voicu G; 'Medical and Pharmaceutical Bionanotechnologies' Laboratory, Institute of Cellular Biology and Pathology 'Nicolae Simionescu' of the Romanian Academy, 050568, Bucharest, Romania., Mocanu CA; 'Medical and Pharmaceutical Bionanotechnologies' Laboratory, Institute of Cellular Biology and Pathology 'Nicolae Simionescu' of the Romanian Academy, 050568, Bucharest, Romania., Safciuc F; 'Medical and Pharmaceutical Bionanotechnologies' Laboratory, Institute of Cellular Biology and Pathology 'Nicolae Simionescu' of the Romanian Academy, 050568, Bucharest, Romania., Anghelache M; 'Medical and Pharmaceutical Bionanotechnologies' Laboratory, Institute of Cellular Biology and Pathology 'Nicolae Simionescu' of the Romanian Academy, 050568, Bucharest, Romania., Deleanu M; 'Liquid and Gas Chromatography' Laboratory, Institute of Cellular Biology and Pathology 'Nicolae Simionescu' of the Romanian Academy, 050568, Bucharest, Romania., Cecoltan S; 'Medical and Pharmaceutical Bionanotechnologies' Laboratory, Institute of Cellular Biology and Pathology 'Nicolae Simionescu' of the Romanian Academy, 050568, Bucharest, Romania., Pinteala M; Centre of Advanced Research in Bionanoconjugates and Biopolymers, 'Petru Poni' Institute of Macromolecular Chemistry, 700487, Iasi, Romania., Uritu CM; Centre of Advanced Research in Bionanoconjugates and Biopolymers, 'Petru Poni' Institute of Macromolecular Chemistry, 700487, Iasi, Romania.; Advanced Centre for Research-Development in Experimental Medicine, Grigore T. Popa University of Medicine and Pharmacy of Iasi, 700115, Iasi, Romania., Droc I; Central Military Hospital 'Dr. Carol Davila', Cardiovascular Surgery Clinic, Bucharest, Romania., Simionescu M; 'Medical and Pharmaceutical Bionanotechnologies' Laboratory, Institute of Cellular Biology and Pathology 'Nicolae Simionescu' of the Romanian Academy, 050568, Bucharest, Romania., Manduteanu I; 'Medical and Pharmaceutical Bionanotechnologies' Laboratory, Institute of Cellular Biology and Pathology 'Nicolae Simionescu' of the Romanian Academy, 050568, Bucharest, Romania., Calin M; 'Medical and Pharmaceutical Bionanotechnologies' Laboratory, Institute of Cellular Biology and Pathology 'Nicolae Simionescu' of the Romanian Academy, 050568, Bucharest, Romania.
المصدر: Materials today. Bio [Mater Today Bio] 2023 Mar 28; Vol. 20, pp. 100620. Date of Electronic Publication: 2023 Mar 28 (Print Publication: 2023).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Ltd Country of Publication: England NLM ID: 101757228 Publication Model: eCollection Cited Medium: Internet ISSN: 2590-0064 (Electronic) Linking ISSN: 25900064 NLM ISO Abbreviation: Mater Today Bio Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: [London] : Elsevier Ltd., [2019]-
مستخلص: Runx2 is a key transcription factor involved in valvular interstitial cells (VIC) osteodifferentiation, a process actively entwined with the calcific aortic valve disease (CAVD). We hypothesize that a strategy intended to silence Runx2 could be a valuable novel therapeutic option for CAVD. To this intent, we aimed at (i) developing targeted nanoparticles for efficient delivery of short hairpin (sh)RNA sequences specific for Runx2 to the aortic valve employing a relevant mouse model for CAVD and (ii) investigate their therapeutic potential in osteoblast-differentiated VIC (oVIC) cultivated into a 3D scaffold. Since collagen IV was used as a target, a peptide that binds specifically to collagen IV (Cp) was conjugated to the surface of lipopolyplexes encapsulating shRNA-Runx2 (Cp-LPP/shRunx2). The results showed that Cp-LPP/shRunx2 were (i) cytocompatible; (ii) efficiently taken up by 3D-cultured oVIC; (iii) diminished the osteodifferentiation of human VIC (cultured in a 3D hydrogel-derived from native aortic root) by reducing osteogenic molecules expression, alkaline phosphatase activity, and calcium concentration; and (iv) were recruited in aortic valve leaflets in a murine model of atherosclerosis. Taken together, these data recommend Cp-LPP/shRunx2 as a novel targeted nanotherapy to block the progression of CAVD, with a good perspective to be introduced in practical use.
Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(© 2023 The Authors.)
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فهرسة مساهمة: Keywords: Calcific aortic valve disease; Collagen IV; Lipopolyplexes; Runx2; Valvular interstitial cells; shRNA
تواريخ الأحداث: Date Created: 20230417 Latest Revision: 20230418
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC10102408
DOI: 10.1016/j.mtbio.2023.100620
PMID: 37063777
قاعدة البيانات: MEDLINE
الوصف
تدمد:2590-0064
DOI:10.1016/j.mtbio.2023.100620