PEG shielded MMP sensitive CPPs for efficient and tumor specific gene delivery in vivo.
J Control Release
; 209: 238-47, 2015 Jul 10.
Article
en En
| MEDLINE
| ID: mdl-25935707
ABSTRACT
Gene therapy has great potential to treat a range of different diseases, such as cancer. For that therapeutic gene can be inserted into a plasmid vector and delivered specifically to tumor cells. The most frequently used applications utilize lipoplex and polyplex approaches where DNA is non-covalently condensed into nanoparticles. However, lack of in vivo efficacy is the major concern that hinders translation of such gene therapeutic applications into clinics. In this work we introduce a novel method for in vivo delivery of plasmid DNA (pDNA) and efficient tumor-specific gene induction using intravenous (i.v) administration route. To achieve this, we utilize a cell penetrating peptide (CPP), PepFect14 (PF14), double functionalized with polyethylene glycol (PEG) and a matrix metalloprotease (MMP) substrate. We show that this delivery vector effectively forms nanoparticles, where the condensed CPP and pDNA are shielded by the PEG, in an MMP-reversible manner. Administration of the complexes results in efficient induction of gene expression specifically in tumors, avoiding normal tissues. This strategy is a potent gene delivery platform that can be used for tumor-specific induction of a therapeutic gene.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Polietilenglicoles
/
Técnicas de Transferencia de Gen
/
Metaloproteinasa 2 de la Matriz
/
Lipopéptidos
/
Péptidos de Penetración Celular
/
Neoplasias
Tipo de estudio:
Diagnostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Control Release
Asunto de la revista:
FARMACOLOGIA
Año:
2015
Tipo del documento:
Article