Nanocarriers of ShRNA-Runx2 Directed to Collagen IV As a Nanotherapeutic System to Target Calcific Aortic Valve Disease

Overview

Journal Mater Today Bio

Specialty Biomedical Engineering

Date 2023 Apr 17

PMID 37063777

Authors

Geanina Voicu

Cristina Ana Mocanu

Florentina Safciuc

Maria Anghelache

Mariana Deleanu

Sergiu Cecoltan

Mariana Pinteala

Cristina Mariana Uritu

Ionel Droc

Maya Simionescu

Ileana Manduteanu

Manuela Calin

Affiliations

Soon will be listed here.

Abstract

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.

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