Reprogramming activated hepatic stellate cells by siRNA-loaded nanocarriers reverses liver fibrosis in mice.

Mice Animals Hepatic Stellate Cells / metabolism RNA, Small Interfering / metabolism Hedgehog Proteins / metabolism Liver Cirrhosis / drug therapy Nanoparticles / chemistry Liver / metabolism
Clinical translation Hepatic stellate cells Lipid nanoparticles Liver fibrosis siRNA

Journal

Journal of controlled release : official journal of the Controlled Release Society
ISSN: 1873-4995
Titre abrégé: J Control Release
Pays: Netherlands
ID NLM: 8607908

Informations de publication

Date de publication:
09 2023
Historique:
received: 10 05 2023
revised: 07 08 2023
accepted: 11 08 2023
medline: 11 9 2023
pubmed: 15 8 2023
entrez: 14 8 2023
Statut: ppublish

Résumé

We report on a novel strategy for treating liver fibrosis through reprogramming activated Hepatic Stellate Cells (aHSCs) into quiescent Hepatic Stellate Cells (qHSCs) using siRNA-loaded lipid nanoparticles (LNPs). The in vivo screening of an array of molecularly-diverse ionizable lipids identified two candidates, CL15A6 and CL15H6, with a high siRNA delivery efficiency to aHSCs. Optimization of the composition and physico-chemical properties of the LNPs enabled the ligand-free, selective, and potent siRNA delivery to aHSCs post intravenous administration, with a median effective siRNA dose (ED

Identifiants

DOI: 10.1016/j.jconrel.2023.08.021 PMID: 37579975
pubmed: 37579975
pii: S0168-3659(23)00520-5
doi: 10.1016/j.jconrel.2023.08.021
pii:
doi:

Substances chimiques

RNA, Small Interfering 0
Hedgehog Proteins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

592-603

Informations de copyright

Copyright © 2023 Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest M.A. Younis, Y. Sato, and H. Harashima are co-inventors in patent applications for the intellectual property associated with this work, which have been submitted to the World Intellectual Property Organization (WIPO)(Application no. PCT/JP2023/9082) and Japan Patent Office, Tokyo, Japan (Application no. 2022–121,626). The authors report no further conflict of interests regarding this work.

Auteurs

Mahmoud A Younis (MA)

Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan; Department of Industrial Pharmacy, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt. Electronic address: mahmoudyounis@aun.edu.eg.

Yusuke Sato (Y)

Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.

Yaser H A Elewa (YHA)

Department of Histology and Cytology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44511, Egypt; Graduate School of Veterinary Medicine, Hokkaido University, Kita-18, Nishi-9, Kita-ku, Sapporo 060-0818, Japan.

Hideyoshi Harashima (H)

Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan. Electronic address: harasima@pharm.hokudai.ac.jp.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Reprogramming activated hepatic stellate cells...
questionsmedicales.fr › Eucaryotes › Animaux › Reprogramming activated hepatic stellate cells...
questionsmedicales.fr › Cellules › Cellules étoilées du foie › Reprogramming activated hepatic stellate cells...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN non traduit › Petit ARN non traduit › Petit ARN interférent › Reprogramming activated hepatic stellate cells...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Protéines Hedgehog › Reprogramming activated hepatic stellate cells...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Fibrose › Cirrhose du foie › Reprogramming activated hepatic stellate cells...
questionsmedicales.fr › Technologie, industrie et agriculture › Produits manufacturés › Nanostructures › Nanoparticules › Reprogramming activated hepatic stellate cells...
questionsmedicales.fr › Système digestif › Foie › Reprogramming activated hepatic stellate cells...