Switching the intracellular pathway and enhancing the therapeutic efficacy of small interfering RNA by auroliposome.
Journal
Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
11
12
2019
accepted:
09
06
2020
entrez:
4
8
2020
pubmed:
4
8
2020
medline:
12
4
2022
Statut:
epublish
Résumé
Gene silencing using small-interfering RNA (siRNA) is a viable therapeutic approach; however, the lack of effective delivery systems limits its clinical translation. Herein, we doped conventional siRNA-liposomal formulations with gold nanoparticles to create "auroliposomes," which significantly enhanced gene silencing. We targeted MICU1, a novel glycolytic switch in ovarian cancer, and delivered MICU1-siRNA using three delivery systems-commercial transfection agents, conventional liposomes, and auroliposomes. Low-dose siRNA via transfection or conventional liposomes was ineffective for MICU1 silencing; however, in auroliposomes, the same dose gave >85% gene silencing. Efficacy was evident from both in vitro growth assays of ovarian cancer cells and in vivo tumor growth in human ovarian cell line-and patient-derived xenograft models. Incorporation of gold nanoparticles shifted intracellular uptake pathways such that liposomes avoided degradation within lysosomes. Auroliposomes were nontoxic to vital organs. Therefore, auroliposomes represent a novel siRNA delivery system with superior efficacy for multiple therapeutic applications.
Identifiants
pubmed: 32743073
doi: 10.1126/sciadv.aba5379
pii: aba5379
pmc: PMC7375829
doi:
Substances chimiques
Liposomes
0
RNA, Small Interfering
0
Gold
7440-57-5
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
eaba5379Subventions
Organisme : NCI NIH HHS
ID : R01 CA260449
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA213278
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA136494
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA225520
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA225500
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM103639
Pays : United States
Informations de copyright
Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).
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