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
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

1132-1151

Informations de copyright

Copyright © 2020 Elsevier B.V. All rights reserved.

Auteurs

Francesca Perrone (F)

Department of Life Sciences, Cattinara University Hospital, Trieste University, Strada di Fiume 447, Trieste I-34149, Italy.

Emanuela Fabiola Craparo (EF)

Department of Scienze e Tecnologie Biologiche, Chimiche, Farmaceutiche (STEBICEF), Lab of Biocompatible Polymers, University of Palermo, via Archirafi 32, Palermo 90123, Italy.

Maja Cemazar (M)

Department of Experimental Oncology, Institute of Oncology Ljubljana, Zaloska 2, Ljubljana SI-1000, Slovenia; Faculty of Health Sciences, University of Primorska, Polje 42, SI-, Izola 6310, Slovenia.

Urska Kamensek (U)

Department of Experimental Oncology, Institute of Oncology Ljubljana, Zaloska 2, Ljubljana SI-1000, Slovenia.

Salvatore Emanuele Drago (SE)

Department of Scienze e Tecnologie Biologiche, Chimiche, Farmaceutiche (STEBICEF), Lab of Biocompatible Polymers, University of Palermo, via Archirafi 32, Palermo 90123, Italy.

Barbara Dapas (B)

Department of Life Sciences, Cattinara University Hospital, Trieste University, Strada di Fiume 447, Trieste I-34149, Italy.

Bruna Scaggiante (B)

Department of Life Sciences, Cattinara University Hospital, Trieste University, Strada di Fiume 447, Trieste I-34149, Italy.

Fabrizio Zanconati (F)

Department of Medical, Surgical and Health Sciences, University of Trieste, Cattinara Hospital, Strada di Fiume, Trieste 447, Italy.

Debora Bonazza (D)

Department of Medical, Surgical and Health Sciences, University of Trieste, Cattinara Hospital, Strada di Fiume, Trieste 447, Italy.

Mario Grassi (M)

Department of Engineering and Architecture, University of Trieste, Via Valerio 6/A, Trieste I 34127, Italy.

Nhung Truong (N)

Stem Cell Research and Application Laboratory - VNUHCM - University of Science, Ho Chi Minh city, Viet Nam.

Gabriele Pozzato (G)

Department of Medical, Surgical and Health Sciences, University of Trieste, Cattinara Hospital, Strada di Fiume, Trieste 447, Italy.

Rossella Farra (R)

Department of Life Sciences, Cattinara University Hospital, Trieste University, Strada di Fiume 447, Trieste I-34149, Italy. Electronic address: rfarra@units.it.

Gennara Cavallaro (G)

Department of Scienze e Tecnologie Biologiche, Chimiche, Farmaceutiche (STEBICEF), Lab of Biocompatible Polymers, University of Palermo, via Archirafi 32, Palermo 90123, Italy. Electronic address: gennara.cavallaro@unipa.it.

Gabriele Grassi (G)

Department of Life Sciences, Cattinara University Hospital, Trieste University, Strada di Fiume 447, Trieste I-34149, Italy; Department of Medical, Surgical and Health Sciences, University of Trieste, Cattinara Hospital, Strada di Fiume, Trieste 447, Italy.

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Classifications MeSH