A gene-delivery system specific for hepatoma cells and an intracellular kinase signal based on human liver-specific bionanocapsules and signal-responsive artificial polymer.
Recently, our group has proposed a novel gene-regulation system responding to cAMP-dependent protein kinase (PKA) that has been applied to living cells. In this study, human liver-specific bionanocapsules (BNCs) are used as a gene-delivery system to increase transfection efficiency and to target specific cell types. BNCs can efficiently deliver a target gene to human hepatocytes and hepatoma cells in vitro or in vivo. The combination of a signal-responsive gene-delivery system with BNCs led to an increase in the transfection efficiency and selectivity for hepatoma cells. Expression from the delivered gene was identified from PKA-activated hepatoma cells (HepG2), but not from colon tumor cells (WiDr). These results show that the combination of a gene-regulation system responding to an intracellular signal with BNC can be used for the selective treatment of human hepatoma cells.
Oishi
Jun
J
Department of Applied Chemistry, Faculty of Engineering, Kyushu University, 744 Motooka, Nishi-Ku, Fukuoka 819-0395, Japan.
Jung
Joohee
J
Tsuchiya
Akira
A
Toita
Riki
R
Kang
Jeong-Hun
JH
Mori
Takeshi
T
Niidome
Takuro
T
Tanizawa
Katsuyuki
K
Kuroda
Shun'ichi
S
Katayama
Yoshiki
Y
D000178:Acrylamides / Q000737:chemistry; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000235:genetics / Q000628:therapy; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004789:Enzyme Activation; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D015316:Genetic Therapy; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000628:therapy; D053769:Nanocapsules; D009842:Oligopeptides / Q000737:chemistry; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection / Q000379:methods*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism
D000178:Acrylamides; C096362:L protein, hepatitis B virus; D053769:Nanocapsules; D009842:Oligopeptides; D011108:Polymers; D014759:Viral Envelope Proteins; D011092:Polyethylene Glycols; C037642:kemptide; C067295:N-isopropylacrylamide; D017868:Cyclic AMP-Dependent Protein Kinases