Polymer-DNA Hybrid Nanoparticles Based on Folate-Polyethylenimine-block-poly(L-lactide)

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• 作者：Chau-Hui Wang and Ging-Ho Hsiue
• 刊名：Bioconjugate Chemistry
• 出版年：2005
• 出版时间：March 2005
• 年：2005
• 卷：16
• 期：2
• 页码：391 - 396
• 全文大小：328K
• 年卷期：v.16,no.2(March 2005)
• ISSN：1520-4812

文摘

The ability of amphiphilic block copolymers that consist of polyethylenimine (PEI) and poly(L-lactide)(PLLA) to modulate the delivery of plasmid DNA was evaluated. Folate-polyethylenimine-block-poly(L-lactide) (folate-PEI-PLLA) was synthesized by linking folic acid and PLLA to PEI diamine.Water-soluble polycation PEI provides gene-loading capability. Additionally, PEI is considered to exhibithigh transfection efficiency and endosomal disrupting capacity. Hydrophobic PLLA that is incorporatedinto the gene delivery vector is believed to enhance the cell interactions and tissue permeability ofthe delivery system. Polymeric carrier containing folic acid is expected to be able to identify tumorsurface receptors and transfect cells by receptor-mediated endocytosis. The results of agaroseretardation assay indicated that the folate-PEI-PLLA began to form polyplexes at a polymer/DNAweight ratio (P/D) of over 10, whereas branched polyethylenimine (B-PEI) formed polyplexes withDNA at a ratio of above 1. The spherical particle morphology was supplemented with a particle sizeof approximately 100 nm at 10 P/D ratio. The results indicated that folate-PEI-PLLA with properPEI/PLLA ratio effectively reduced cytotoxicity and maintained acceptable transfection efficiency. Lowcytotoxicity of the folate-PEI-PLLA gives an advantage to high-dose administration.