Dual-ligand effect of transferrin and transforming growth factor alpha on polyethyleneimine-mediated gene delivery.
In order to enhance the internalization of exogenous gene and add cell specificity to non-viral vectors, receptor-binding elements have been widely utilized to mimic the virus infection. Herein, for the purpose of intensifying the effects of the ligand on gene delivery, dual receptor-binding elements, transferrin (Tf) and transforming growth factor alpha (TGFalpha), were introduced into the polyethyleneimine polyplex. The transfection and internalization efficiency by dual Tf- and TGFalpha-introduced polyplex (Tf&TGFalpha-polyplex) was examined in A549 and CHO-K1 cells, respectively. In A549, Tf&TGFalpha-polyplex had higher transfection efficiency when compared to that by single Tf- or TGFalpha-introduced polyplex (Tf-polyplex and TGFalpha-polyplex), respectively, while no enhancement was observed in CHO-K1. Moreover, in A549, the internalization efficiency of dual Tf&TGFalpha-polyplex was higher than that of single Tf- and TGFalpha-polyplex. In contrast, in CHO-K1, no difference in internalization efficiency was observed. In the presence of excess free transferrin or TGFalpha, the internalization efficiency of Tf&TGFalpha-polyplex was strongly inhibited only in A549, not in CHO-K1. In summary, the enhancement of internalization efficiency by dual ligands is an important factor for improving transfection efficiency. In addition, the effect of dual ligands depends on cell species; receptor-mediated and efficient internalization may be related to this enhanced transfection efficiency.
Kakimoto
Shinji
S
Department of Applied Chemistry and Bioengineering, Graduate School of Engineering, Osaka City University, Sugimoto, Sumiyoshi-ku, Osaka, Japan.
Moriyama
Tetsuji
T
Tanabe
Toshizumi
T
Shinkai
Seiji
S
Nagasaki
Takeshi
T
D000818:Animals; D019921:Biotinylation; D016466:CHO Cells; D002417:Cattle; D045744:Cell Line, Tumor; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D005822:Genetic Vectors; D006801:Humans; D007097:Imines / Q000737:chemistry* / Q000378:metabolism; D008024:Ligands; D008156:Luciferases / Q000378:metabolism; D008970:Molecular Weight; D011095:Polyethylenes / Q000737:chemistry* / Q000378:metabolism; D011990:Receptors, Transferrin / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000378:metabolism; D014162:Transfection; D014168:Transferrin / Q000494:pharmacology*; D016211:Transforming Growth Factor alpha / Q000494:pharmacology*
D007097:Imines; D008024:Ligands; D011095:Polyethylenes; D011990:Receptors, Transferrin; D014168:Transferrin; D016211:Transforming Growth Factor alpha; C505405:poly(ethylene imine); D012710:Serum Albumin, Bovine; D004247:DNA; D008156:Luciferases; D066246:ErbB Receptors