Targeted delivery of siRNAs against hepatocellular carcinoma-related genes by a galactosylated polyaspartamide copolymer.
ASGPR targeted delivery
E2F1
Eukaryotic elongation Factor 1A
Hepatocellular carcinoma
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:
10 02 2021
10 02 2021
Historique:
received:
22
07
2020
revised:
07
11
2020
accepted:
11
11
2020
pubmed:
20
11
2020
medline:
8
7
2021
entrez:
19
11
2020
Statut:
ppublish
Résumé
Given the lack of effective treatments for Hepatocellular carcinoma (HCC), the development of novel therapeutic approaches is very urgent. Here, siRNAs were delivered to HCC cells by a synthetic polymer containing α,β-poly-(N-2-hydroxyethyl)-D,L-aspartamide-(PHEA) derivatized with diethylene triamine (DETA) and bearing in the side chain galactose (GAL) linked via a polyethylene glycol (PEG) to obtain (PHEA-DETA-PEG-GAL, PDPG). The GAL residue allows the targeting to the asialo-glycoprotein receptor (ASGPR), overexpressed in HCC cells compared to normal hepatocytes. Uptake studies performed using a model siRNA or a siRNA targeted against the enhanced green fluorescence protein, demonstrated the PDPG specific delivery of siRNA to HuH7 cells, a human cellular model of HCC. GAL-free copolymer (PHEA-DETA-PEG-NH
Identifiants
pubmed: 33212117
pii: S0168-3659(20)30669-6
doi: 10.1016/j.jconrel.2020.11.020
pii:
doi:
Substances chimiques
Polymers
0
RNA, Small Interfering
0
Galactose
X2RN3Q8DNE
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1132-1151Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.