Exploiting endocytosis for transfection of mRNA for cytoplasmatic delivery using cationic gold nanoparticles.
cationic
gene therapeutics
gold nanoparticles
safety
transfection
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2023
2023
Historique:
received:
20
12
2022
accepted:
21
04
2023
medline:
29
5
2023
pubmed:
25
5
2023
entrez:
25
5
2023
Statut:
epublish
Résumé
Gene therapy holds promise to cure various diseases at the fundamental level. For that, efficient carriers are needed for successful gene delivery. Synthetic 'non-viral' vectors, as cationic polymers, are quickly gaining popularity as efficient vectors for transmitting genes. However, they suffer from high toxicity associated with the permeation and poration of the cell membrane. This toxic aspect can be eliminated by nanoconjugation. Still, results suggest that optimising the oligonucleotide complexation, ultimately determined by the size and charge of the nanovector, is not the only barrier to efficient gene delivery. We herein develop a comprehensive nanovector catalogue comprising different sizes of Au NPs functionalized with two different cationic molecules and further loaded with mRNA for its delivery inside the cell. Tested nanovectors showed safe and sustained transfection efficiencies over 7 days, where 50 nm Au NPs displayed the highest transfection rates. Remarkably, protein expression was increased when nanovector transfection was performed combined with chloroquine. Cytotoxicity and risk assessment demonstrated that nanovectors are safe, ascribed to lesser cellular damage due to their internalization and delivery via endocytosis. Obtained results may pave the way to design advanced and efficient gene therapies for safely transferring oligonucleotides.
Identifiants
pubmed: 37228592
doi: 10.3389/fimmu.2023.1128582
pmc: PMC10205015
doi:
Substances chimiques
Gold
7440-57-5
RNA, Messenger
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1128582Informations de copyright
Copyright © 2023 Gustà, Edel, Salazar, Alvarez-Palomo, Juan, Broggini, Damia, Bigini, Corbelli, Fiordaliso, Barbul, Korenstein, Bastús and Puntes.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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