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Core-Shell Polymer-Based Nanoparticles Deliver miR-155-5p to Endothelial Cells.

Authors :
Antunes JC
Benarroch L
Moraes FC
Juenet M
Gross MS
Aubart M
Boileau C
Caligiuri G
Nicoletti A
Ollivier V
Chaubet F
Letourneur D
Chauvierre C
Source :
Molecular therapy. Nucleic acids [Mol Ther Nucleic Acids] 2019 Sep 06; Vol. 17, pp. 210-222. Date of Electronic Publication: 2019 Jun 04.
Publication Year :
2019

Abstract

Heart failure occurs in over 30% of the worldwide population and most commonly originates from cardiovascular diseases such as myocardial infarction. microRNAs (miRNAs) target and silence specific mRNAs, thereby regulating gene expression. Because the endogenous miR-155-5p has been ascribed to vasculoprotection, loading it onto positively charged, core-shell poly(isobutylcyanoacrylate) (PIBCA)-polysaccharide nanoparticles (NPs) was attempted. NPs showed a decrease (p < 0.0001) in surface electrical charge (ζ potential), with negligible changes in size or shape when loaded with the anionic miR-155-5p. Presence of miR-155-5p in loaded NPs was further quantified. Cytocompatibility up to 100 μg/mL of NPs for 2 days with human coronary artery endothelial cells (hCAECs) was documented. NPs were able to enter hCAECs and were localized in the endoplasmic reticulum (ER). Expression of miR-155-5p was increased within the cells by 75-fold after 4 hours of incubation (p < 0.05) and was still noticeable at day 2. Differences between loaded NP-cultured cells and free miRNA, at days 1 (p < 0.05) and 2 (p < 0.001) suggest the ability of prolonged load release in physiological conditions. Expression of miR-155-5p downstream target BACH1 was decreased in the cells by 4-fold after 1 day of incubation (p < 0.05). This study is a first proof of concept that miR-155-5p can be loaded onto NPs and remain intact and biologically active in endothelial cells (ECs). These nanosystems could potentially increase an endogenous cytoprotective response and decrease damage within infarcted hearts.<br /> (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
2162-2531
Volume :
17
Database :
MEDLINE
Journal :
Molecular therapy. Nucleic acids
Publication Type :
Academic Journal
Accession number :
31265949
Full Text :
https://doi.org/10.1016/j.omtn.2019.05.016