Polyethylenimine-grafted copolymer of poly(l-lysine) and poly(ethylene glycol) for gene delivery.
Biomaterials
; 32(6): 1694-705, 2011 Feb.
Article
en En
| MEDLINE
| ID: mdl-21093048
ABSTRACT
A major challenge in gene therapy is the development of effective gene delivery vectors with low toxicity. In the present study, linear poly(ethylenimine) (lPEI) with low molecular weight was grafted onto the block copolymer (PPL) of poly(l-lysine) (PLL) and poly(ethylene glycol)(PEG), yielding a ternary copolymer PEG-b-PLL-g-lPEI (PPI) for gene delivery. In such molecular design, PLL, lPEI and PEG blocks were expected to render the vector biodegradability, proton buffering capacity, low cationic toxicity and potentially long circulation in vivo, respectively. Given proper control of molecular composition, the copolymers demonstrated lower cytotoxicity, proton buffering capacity, ability to condense pDNA and mediate effective gene transfection in various cell lines. With folate as an exemplary targeting ligand, the FA-PPI/pDNA complex showed much higher transgene activity than its nontargeting counterpart for both reporter and therapeutic genes in folate receptor(FR)-positive cells. FA-PPI mediated effective transfection of the TNF-related apoptosis-inducing ligand gene (TRAIL) in human hepatoma Bel 7402 cells, leading to cell apoptosis and great suppression of cell viability. Our results indicate that the copolymers might be a promising vector combining low cytotoxicity, biodegradability, and high gene transfection efficiency.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Polietilenglicoles
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Polietileneimina
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Polímeros
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Terapia Genética
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Vectores Genéticos
Límite:
Humans
Idioma:
En
Revista:
Biomaterials
Año:
2011
Tipo del documento:
Article
País de afiliación:
China