Dexamethasone-conjugated low molecular weight polyethylenimine as a nucleus-targeting lipopolymer gene carrier.
Dexamethasone, a glucocorticoid steroid, can dilate the nuclear pore complexes and translocate into the nucleus when it is bound to its glucocorticoid receptor, suggesting that the transport of DNA into the nucleus may be facilitated by the reagent. In this research, dexamethasone was conjugated to low molecular weight polyethylenimine (2 kDa) for efficient translocation of the polymer/DNA complex into the nucleus. Polyethylenimine (PEI)-dexamethasone (PEI-Dexa) was synthesized by one-step reaction using the Traut's reagent. In gel retardation assay, the PEI-Dexa/DNA complex was completely retarded at or above 0.3/1 weight ratio (polymer/DNA). The average size distributions and zeta-potential values of the complexes were measured at various weight ratios. In vitro transfection assay showed that the PEI-Dexa/DNA complex had higher gene delivery efficiency compared to PEI 2kDa/DNA complex. The localization of PEI-Dexa/plasmid DNA complexes in the nucleus was confirmed by using total internal reflection fluorescence and Nomarski differential interference contrast microscope as well as confocal microscope. Therefore, with efficient nuclear translocation and low cytotoxicity, PEI-Dexa may be useful for nonviral gene therapy.
Mi Bae
Yun
Y
Department of Biochemistry, Chungnam National University, Daejeon, Korea.
Choi
Hye
H
Lee
Seungah
S
Ho Kang
Seong
S
Tae Kim
Young
Y
Nam
Kihoon
K
Sang Park
Jong
J
Lee
Minhyung
M
Sig Choi
Joon
J
D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000737:chemistry / Q000235:genetics; D003907:Dexamethasone / Q000737:chemistry* / Q000633:toxicity; D004587:Electrophoresis, Agar Gel; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D008970:Molecular Weight; D010957:Plasmids / Q000737:chemistry / Q000235:genetics; D011094:Polyethyleneimine / Q000737:chemistry*; D014162:Transfection
D008055:Lipids; D003907:Dexamethasone; D011094:Polyethyleneimine; D004247:DNA