Polymer-DNA hybrid nanoparticles based on folate-polyethylenimine-block-poly(L-lactide).
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 exhibit high transfection efficiency and endosomal disrupting capacity. Hydrophobic PLLA that is incorporated into the gene delivery vector is believed to enhance the cell interactions and tissue permeability of the delivery system. Polymeric carrier containing folic acid is expected to be able to identify tumor surface receptors and transfect cells by receptor-mediated endocytosis. The results of agarose retardation assay indicated that the folate-PEI-PLLA began to form polyplexes at a polymer/DNA weight ratio (P/D) of over 10, whereas branched polyethylenimine (B-PEI) formed polyplexes with DNA at a ratio of above 1. The spherical particle morphology was supplemented with a particle size of approximately 100 nm at 10 P/D ratio. The results indicated that folate-PEI-PLLA with proper PEI/PLLA ratio effectively reduced cytotoxicity and maintained acceptable transfection efficiency. Low cytotoxicity of the folate-PEI-PLLA gives an advantage to high-dose administration.
Wang
Chau-Hui
CH
Department of Chemical Engineering, National Tsing Hua University, Hsinchu, 300 Taiwan, ROC.
Hsiue
Ging-Ho
GH
D002470:Cell Survival; D004247:DNA / Q000493:pharmacokinetics*; D005492:Folic Acid / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D008156:Luciferases / Q000235:genetics; D049329:Nanostructures; D010957:Plasmids / Q000493:pharmacokinetics; D011091:Polyesters / Q000737:chemistry; D011094:Polyethyleneimine / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D014162:Transfection / Q000379:methods*
D011091:Polyesters; D011108:Polymers; C033616:poly(lactide); D011094:Polyethyleneimine; D004247:DNA; D005492:Folic Acid; D008156:Luciferases