Branched polyethylenimine-based PKCα-responsive gene carriers.
We examined in vitro performance of the branched polyethylenimine (bPEI)-based gene carriers which respond to cancer-specific activation of protein kinase Cα (PKCα) to express plasmid DNA. The carriers were synthesized straightforward by using amide bond formation between a peptide terminal carboxyl and a primary amine group of bPEI. To examine the effect of the peptide contents in the carrier, we prepared several carriers with various peptide contents. The obtained polymers form polyplexes with tighter condensation of plasmid DNA than our previous gene carriers. After internalization of the polyplexes via endocytosis, the polyplexes effectively escaped from the endosome into cytosol. Then, the polyplexes showed a clear-cut response to PKCα to release plasmid DNA for gene expression. We determined the optimum contents of the peptides in carriers as 5 mol% to achieve the clear-cut response to PKCα.
a Graduate School of Systems Life Sciences, Kyushu University , 744 Motooka , Nishi-ku , Fukuoka , 819-0395 , Japan.
Yuta
Y
Nakamura
Chan Woo
CW
Kim
Akira
A
Tsuchiya
Satoshi
S
Kushio
Takanobu
T
Nobori
Kai
K
Li
Eun Kyung
EK
Lee
Guo Xi
GX
Zhao
Daiki
D
Funamoto
Takuro
T
Niidome
Takeshi
T
Mori
Yoshiki
Y
Katayama
D001692:Biological Transport; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D010455:Peptides / Q000737:chemistry; D011094:Polyethyleneimine / Q000737:chemistry* / Q000378:metabolism; D051571:Protein Kinase C-alpha / Q000378:metabolism*; D014162:Transfection / Q000379:methods*
D004337:Drug Carriers; D010455:Peptides; D011094:Polyethyleneimine; D051571:Protein Kinase C-alpha