The development of a gene vector electrostatically assembled with a polysaccharide capsule.
The purpose of this study was to develop a gene vector electrostatically assembled with a polysaccharide capsule. We used pDNA/polyethylenimine (PEI) complexes as efficient non-viral vectors. The pDNA/PEI complex was electrostatically encapsulated with various polysaccharides such as fucoidan, lambda-carrageenan, xanthan gum, alginic acid, hyaluronic acid, and chondroitin sulfate (CS). The pDNA/PEI complex was shown as nanoparticles with positive zeta-potential, although the ternary complexes encapsulated with polysaccharides were shown as nanoparticles with negative zeta-potential. The pDNA/PEI complex showed high agglutination activity and cytotoxicity, although the ternary complexes encapsulated with polysaccharides had no agglutination activities and lower cytotoxicities. The pDNA/PEI complex showed high uptake and high transgene efficiency in B16-F10 cells. On the other hand, most of the ternary complexes show little uptake and gene expression. The ternary complex encapsulated by CS, however, showed comparable transgene efficiency to the pDNA/PEI complex. The uptake and gene expression of the ternary complex encapsulated by CS were significantly inhibited by hypothermia and the addition of CS, suggesting that the ternary complex was taken by CS-specific receptor-mediated energy-dependent process.
Kurosaki
Tomoaki
T
Department of Hospital Pharmacy, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
Kitahara
Takashi
T
Kawakami
Shigeru
S
Nishida
Koyo
K
Nakamura
Junzo
J
Teshima
Mugen
M
Nakagawa
Hiroo
H
Kodama
Yukinobu
Y
To
Hideto
H
Sasaki
Hitoshi
H
D000818:Animals; D002214:Capsules; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism; D004586:Electrophoresis; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects; D005822:Genetic Vectors / Q000235:genetics*; D006384:Hemagglutination / Q000187:drug effects; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D010316:Particle Size; D010957:Plasmids / Q000378:metabolism; D011094:Polyethyleneimine / Q000633:toxicity; D011134:Polysaccharides / Q000494:pharmacology*; D055672:Static Electricity; D014162:Transfection / Q000379:methods*; D019076:Transgenes
D002214:Capsules; D011134:Polysaccharides; D011094:Polyethyleneimine; D004247:DNA