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Gene-Directed Enzyme Prodrug Therapy by Dendrimer-Like Mesoporous Silica Nanoparticles against Tumor Cells
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 c...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156333/ https://www.ncbi.nlm.nih.gov/pubmed/34069171 http://dx.doi.org/10.3390/nano11051298 |
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author | Candela-Noguera, Vicente Vivo-Llorca, Gema Díaz de Greñu, Borja Alfonso, María Aznar, Elena Orzáez, Mar Marcos, María Dolores Sancenón, Félix Martínez-Máñez, Ramón |
author_facet | Candela-Noguera, Vicente Vivo-Llorca, Gema Díaz de Greñu, Borja Alfonso, María Aznar, Elena Orzáez, Mar Marcos, María Dolores Sancenón, Félix Martínez-Máñez, Ramón |
author_sort | Candela-Noguera, Vicente |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8156333 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-81563332021-05-28 Gene-Directed Enzyme Prodrug Therapy by Dendrimer-Like Mesoporous Silica Nanoparticles against Tumor Cells Candela-Noguera, Vicente Vivo-Llorca, Gema Díaz de Greñu, Borja Alfonso, María Aznar, Elena Orzáez, Mar Marcos, María Dolores Sancenón, Félix Martínez-Máñez, Ramón Nanomaterials (Basel) Article 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. MDPI 2021-05-14 /pmc/articles/PMC8156333/ /pubmed/34069171 http://dx.doi.org/10.3390/nano11051298 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Candela-Noguera, Vicente Vivo-Llorca, Gema Díaz de Greñu, Borja Alfonso, María Aznar, Elena Orzáez, Mar Marcos, María Dolores Sancenón, Félix Martínez-Máñez, Ramón Gene-Directed Enzyme Prodrug Therapy by Dendrimer-Like Mesoporous Silica Nanoparticles against Tumor Cells |
title | Gene-Directed Enzyme Prodrug Therapy by Dendrimer-Like Mesoporous Silica Nanoparticles against Tumor Cells |
title_full | Gene-Directed Enzyme Prodrug Therapy by Dendrimer-Like Mesoporous Silica Nanoparticles against Tumor Cells |
title_fullStr | Gene-Directed Enzyme Prodrug Therapy by Dendrimer-Like Mesoporous Silica Nanoparticles against Tumor Cells |
title_full_unstemmed | Gene-Directed Enzyme Prodrug Therapy by Dendrimer-Like Mesoporous Silica Nanoparticles against Tumor Cells |
title_short | Gene-Directed Enzyme Prodrug Therapy by Dendrimer-Like Mesoporous Silica Nanoparticles against Tumor Cells |
title_sort | gene-directed enzyme prodrug therapy by dendrimer-like mesoporous silica nanoparticles against tumor cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156333/ https://www.ncbi.nlm.nih.gov/pubmed/34069171 http://dx.doi.org/10.3390/nano11051298 |
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