Biscarbamate cross-linked low molecular weight Polyethylenimine polycation as an efficient intra-cellular delivery cargo for cancer therapy.
J Nanobiotechnology
; 12: 13, 2014 Apr 06.
Article
em En
| MEDLINE
| ID: mdl-24708586
ABSTRACT
BACKGROUND:
A challenge in gene therapy is the efficient delivery of DNA/siRNA to the diseased cells. The physicochemical characteristics of siRNA, such as high molecular weight, negative charges and hydrophilic nature-prevent passive diffusion across the plasma membrane for most cells. A therapeutically feasible carrier for intra-cellular delivery of gene materials should accomplish a series of tasks such as condensing nucleic acid, protecting nucleic acid from leaking in vivo, facilitating endosome escape and releasing DNA/siRNA to the target site. To meet these requirements, an efficient gene vector based on polycation synthesis for siRNA delivery both in vitro and in vivo was developed.RESULTS:
The polymer was synthesized by 1, 4-butanediol bis (chloroformate) and PEI 800 Da to form PEI-Bu which could condense siRNA at the N/P ratio of 38.35 or above. The size of the nanoparticles was 100-300 nm and zeta potential was in the range of 10-30 mV at different N/P ratios. The nanoparticles can achieve the ability of cellular uptake and the silencing efficiency was about 46.63% in SMMC-7721 cell line which was generated to stably express GL3 luciferase gene. The cytotoxicity of the polyplex nanoparticles was almost negligible on SMMC-7721 cells by MTT assay, indicating that the reduced luciferase expression was the effect of RNAi, not the influence of cytotoxicity of polyplexes. The polyplex nanoparticle formulated by PEI-Bu and siRNA at N/P ratio of 115.05 was injected into the SMMC-7721 tumor bearing mice locally and the expression of luciferase can reduce to 63.17% compared with control group.CONCLUSIONS:
Results in this study suggested that PEI-Bu polycation might provide a promising solution for siRNA delivery and had the potential in anti-tumor gene therapy.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Poliaminas
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Polietilenoimina
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Carbamatos
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RNA Interferente Pequeno
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Interferência de RNA
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Nanopartículas
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article