Cationized extracellular vesicles for gene delivery.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
28 10 2024
Historique:
received: 03 05 2024
accepted: 09 10 2024
medline: 29 10 2024
pubmed: 29 10 2024
entrez: 29 10 2024
Statut: epublish

Résumé

Last decade, extracellular vesicles (EVs) attracted a lot of attention as potent versatile drug delivery vehicles. We reported earlier the development of EV-based delivery systems for therapeutic proteins and small molecule chemotherapeutics. In this work, we first time engineered EVs with multivalent cationic lipids for the delivery of nucleic acids. Stable, small size cationized EVs were loaded with plasmid DNA (pDNA), or mRNA, or siRNA. Nucleic acid loaded EVs were efficiently taken up by target cells as demonstrated by confocal microscopy and delivered their cargo to the nuclei in triple negative breast cancer (TNBC) cells and macrophages. Efficient transfection was achieved by engineered cationized EVs formulations of pDNA- and mRNA in vitro. Furthermore, siRNA loaded into cationized EVs showed significant knockdown of the reporter gene in Luc-expressing cells. Overall, multivalent cationized EVs represent a promising strategy for gene delivery.

Identifiants

pubmed: 39468145
doi: 10.1038/s41598-024-75985-y
pii: 10.1038/s41598-024-75985-y
doi:

Substances chimiques

Cations 0
RNA, Small Interfering 0
RNA, Messenger 0
DNA 9007-49-2

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

25818

Subventions

Organisme : Russian Science Foundation
ID : 22-13-00261
Organisme : State Registration Theme
ID : 121041500039-8; 123032300028-0
Organisme : State Registration Theme
ID : 121041500039-8; 123032300028-0
Organisme : State Registration Theme
ID : 121041500039-8; 123032300028-0
Organisme : Eshelman Institute for Innovation grant
ID : UNC EII 29202

Informations de copyright

© 2024. The Author(s).

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Auteurs

Natalia L Klyachko (NL)

Division of Pharmacoengineering and Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599-7362, USA. nlklyachko@gmail.com.
Deparment of Chemical Enzymology, Faculty of Chemistry, Lomonosov Moscow State University, Moscow, Russia. nlklyachko@gmail.com.

Matthew J Haney (MJ)

Division of Pharmacoengineering and Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599-7362, USA.
Center for Nanotechnology in Drug Delivery, Carolina Institute for Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Anton V Lopukhov (AV)

Deparment of Chemical Enzymology, Faculty of Chemistry, Lomonosov Moscow State University, Moscow, Russia.

Irina M Le-Deygen (IM)

Deparment of Chemical Enzymology, Faculty of Chemistry, Lomonosov Moscow State University, Moscow, Russia.

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