Targeted gene delivery mediated by folate-polyethylenimine-block-poly(ethylene glycol) with receptor selectivity.
The folate receptor (FR) is a tumor marker overexpressed in large numbers of cancer cells. Folic acid has high affinity to the FR and retains its binding affinity upon derivatization via its gamma-carboxyl. Therefore, in this article, folate-polyethylenimine-block-poly(ethylene glycol) (FOL-PEI-b-PEG) was designed for specific receptor targeted gene delivery. Physicochemical characterizations of resulting FOL-PEI-b-PEG/DNA complexes in terms of agarose gel electrophoresis, particle size, and zeta potential measurements were investigated. The results indicated that FOL-PEI-b-PEG was able to condense plasmid DNA tightly with a suitable particle size. The cytotoxicity study indicated that the copolymer exhibited less toxicity in comparison with that of 25 kDa PEI. Luciferase assay and green fluorescent protein (GFP) detections were also used to confirm that FOL-PEI-b-PEG could be an effective gene vector. Importantly, transfection efficiency of FOL-PEI-b-PEG with free folic acid was much lower than that of the copolymer without free folic acid on FR-positive HeLa cells, suggesting that FOL-PEI-b-PEG has great potential as a targeting gene vector.
Cheng
Han
H
Key Laboratory of Biomedical Polymers of the Ministry of Education, Department of Chemistry, Wuhan University, Wuhan, P.R. China.
Zhu
Jing-Ling
JL
Zeng
Xuan
X
Jing
Yue
Y
Zhang
Xian-Zheng
XZ
Zhuo
Ren-Xi
RX
D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000737:chemistry* / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D008156:Luciferases / Q000235:genetics; D010316:Particle Size; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics; D011092:Polyethylene Glycols / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry*; D011956:Receptors, Cell Surface / Q000378:metabolism; D014162:Transfection
D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D011956:Receptors, Cell Surface; D049452:Green Fluorescent Proteins; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D004247:DNA; D005492:Folic Acid; D008156:Luciferases