Receptor-mediated gene delivery using polyethylenimine (PEI) coupled with polypeptides targeting FGF receptors on cells surface.
OBJECTIVE
To construct a novel kind of nonviral gene delivery vector based on polyethylenimine (PEI) conjugated with polypeptides derived from ligand FGF with high transfection efficiency and according to tumor targeting ability.


METHODS
The synthetic polypeptides CR16 for binding FGF receptors was conjugated to PEI and the characters of the polypeptides including DNA condensing and particle size were determined. Enhanced efficiency and the targeting specificity of the synthesized vector were investigated in vitro and in vivo.


RESULTS
The polypeptides were successfully coupled to PEI. The new vectors PEI-CR16 could efficiently condense pDNA into particles with around 200 nm diameter. The PEI-CR16/pDNA polyplexes showed significantly greater transgene activity than PEI/pDNA in FGF receptors positive tumor cells in vitro and in vivo gene transfer, while no difference was observed in FGF receptors negative tumor cells. The enhanced transfection efficiency of PEI-CR16 could be blocked by excess free polypeptides.


CONCLUSIONS
The synthesized vector could improve the efficiency of gene transfer and targeting specificity in FGF receptors positive cells. The vector had good prospect for use in cancer gene therapy.
Li
Da
D
Institute of Immunology, Zhejiang University, Hangzhou 310058, China.
Wang
Qing-qing
QQ
Tang
Gu-ping
GP
Huang
Hong-liang
HL
Shen
Fen-ping
FP
Li
Jing-zhong
JZ
Yu
Hai
H
D000818:Animals; D001665:Binding Sites; D002277:Carcinoma / Q000628:therapy; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005346:Fibroblast Growth Factors / Q000378:metabolism; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008024:Ligands; D008113:Liver Neoplasms / Q000628:therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010316:Particle Size; D010455:Peptides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011094:Polyethyleneimine / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000628:therapy*; D017468:Receptors, Fibroblast Growth Factor / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013499:Surface Properties; D014162:Transfection; D014183:Transplantation, Heterologous; D023041:Xenograft Model Antitumor Assays
D008024:Ligands; D010455:Peptides; D017468:Receptors, Fibroblast Growth Factor; D005346:Fibroblast Growth Factors; D011094:Polyethyleneimine