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Gene-Directed Enzyme Prodrug Therapy by Dendrimer-Like Mesoporous Silica Nanoparticles against Tumor Cells

Fecha de publicación:

Autores de CIPF

  • Gema Vivo Llorca

    Autor

  • Elena Aznar Gimeno

    Autor

  • María Dolores Marcos Martínez

    Autor

  • Félix Sancenón Galarza

    Autor

  • Ramón Martínez Mañez

    Autor

Participantes ajenos a CIPF

  • Candela-Noguera, V
  • de Grenu, BD
  • Alfonso, M

Grupos de Investigación

Abstract

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 beta-galactosidase (beta-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 beta-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 beta-gal.

Datos de la publicación

ISSN/ISSNe:
2079-4991, 2079-4991

Nanomaterials  MDPI

Tipo:
Article
Páginas:
-
PubMed:
34069171

Citas Recibidas en Web of Science: 7

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Keywords

  • GDEPT; DMSNs; tumor treatment; drug delivery

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