Dual-targeting non-viral vector based on polyethylenimine improves gene transfer efficiency.
Polyethylenimine (PEI) is the polymer most commonly used for transferring plasmids into eukaryotes, but its gene-transfer efficiency is lower compared to viral vectors. Receptors targeting PEI combined with ligands can enhance efficiency of gene transfer into the corresponding receptor-positive cells. Using the double-receptor-mediated pathway of viral infection, in this study we synthesized a novel non-viral vector based on PEI combined with two peptides recognizing FGF receptors (peptide YC25) and integrins (peptide CP9) on the cell surface. The dual targeting vector showed a physicochemical character similar to that of PEI, such as pDNA formation, particle size, zeta potential and lower toxicity. In vitro gene transfer showed that the dual-receptor targeted vector (YC25-PEI-CP9) exhibited a markedly higher transgene efficiency in cell lines with positive expression of FGF receptors and integrins, compared with single-peptide-modified PEI or unmodified PEI. In the cells with only integrin-positive expression, YC25-PEI-CP9 mediated a higher transgene expression than PEI but lower than CP9-PEI. The corresponding free peptides could inhibit the transgene efficiency of the peptide-coupled PEI. In vivo gene transfer in tumor-bearing nude mice also demonstrated that the dual-targeting vectors showed a significantly enhanced transfection efficiency in tumors with positive expression of FGF receptors and integrins. The synthesized polymer YC25-PEI-CP9 has the prospect to act as a novel kind of non-viral vector in gene therapy.
Li
D
D
Institute of Immunology, Zhejiang University, 388 Yuhangtang Road, Hangzhou 310058, P. R. China.
Tang
G P
GP
Li
J Z
JZ
Kong
Y
Y
Huang
H L
HL
Min
L J
LJ
Zhou
J
J
Shen
F P
FP
Wang
Q Q
QQ
Yu
H
H
D000818:Animals; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000627:therapeutic use; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000627:therapeutic use / Q000633:toxicity; D006801:Humans; D008024:Ligands; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000627:therapeutic use; D011094:Polyethyleneimine / Q000627:therapeutic use*; D014162:Transfection / Q000379:methods
D008024:Ligands; D010455:Peptides; D016222:Fibroblast Growth Factor 2; D011094:Polyethyleneimine