Gene-Directed Enzyme Prodrug Therapy by Dendrimer-Like Mesoporous Silica Nanoparticles against Tumor Cells.
DMSNs
GDEPT
drug delivery
tumor treatment
Journal
Nanomaterials (Basel, Switzerland)
ISSN: 2079-4991
Titre abrégé: Nanomaterials (Basel)
Pays: Switzerland
ID NLM: 101610216
Informations de publication
Date de publication:
14 May 2021
14 May 2021
Historique:
received:
14
04
2021
revised:
06
05
2021
accepted:
10
05
2021
entrez:
2
6
2021
pubmed:
3
6
2021
medline:
3
6
2021
Statut:
epublish
Résumé
We report herein a gene-directed enzyme prodrug therapy (GDEPT) system using gated mesoporous silica nanoparticles (MSNs) in an attempt to combine the reduction of side effects characteristic of GDEPT with improved pharmacokinetics promoted by gated MSNs. The system consists of the transfection of cancer cells with a plasmid controlled by the cytomegalovirus promoter, which promotes β-galactosidase (β-gal) expression from the bacterial gene lacZ (CMV-lacZ). Moreover, dendrimer-like mesoporous silica nanoparticles (DMSNs) are loaded with the prodrug doxorubicin modified with a galactose unit through a self-immolative group (DOXO-Gal) and modified with a disulfide-containing polyethyleneglycol gatekeeper. Once in tumor cells, the reducing environment induces disulfide bond rupture in the gatekeeper with the subsequent DOXO-Gal delivery, which is enzymatically converted by β-gal into the cytotoxic doxorubicin drug, causing cell death. The combined treatment of the pair enzyme/DMSNs-prodrug are more effective in killing cells than the free prodrug DOXO-Gal alone in cells transfected with β-gal.
Identifiants
pubmed: 34069171
pii: nano11051298
doi: 10.3390/nano11051298
pmc: PMC8156333
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : European Regional Development Fund
ID : RTI2018-100910-B-C41
Organisme : European Regional Development Fund
ID : RTI2018-101599-B-C22
Organisme : Ministerio de Ciencia, Innovación y Universidades
ID : RTI2018-101599-B-C22
Organisme : Ministerio de Ciencia, Innovación y Universidades
ID : RTI2018-100910-B-C41
Organisme : Generalitat Valenciana
ID : PROMETEO 2018/024
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