Biocleavable polyrotaxane-plasmid DNA polyplex for enhanced gene delivery.
A biocleavable polyrotaxane, having a necklace-like structure consisting of many cationic alpha-cyclodextrins (alpha-CDs) and a disulfide-introduced poly(ethylene glycol) (PEG), was synthesized and examined as a nonviral gene carrier. The polyrotaxane formed a stable polyplex having positively charged surface even at low charge ratio. This is likely to be due to structural factors of the polyrotaxane, such as the mobile motion of alpha-CDs in the necklace-like structure. Rapid endosomal escape was observed 90 min after transfection. The positively charged surface and the good buffering capacity are advantageous to show the proton sponge effect. The pDNA decondensation occurred through disulfide cleavage of the polyrotaxane and subsequent supramolecular dissociation of the noncovalent linkages between alpha-CDs and PEG. Transfection of the DMAE-SS-PRX polyplex is independent of the amount of free polycation. Those properties played a key role for delivery of pDNA clusters to the nucleus. Therefore, the polyplex nature and the supramolecular dissociation of the polyrotaxane contributed to the enhanced gene delivery.
School of Materials Science and the 21st COE Program, Japan Advanced Institute of Science and Technology, 1-1 Asahidai, Nomi, Ishikawa 923-1292, Japan.
Tooru
T
Ooya
Hak Soo
HS
Choi
Atsushi
A
Yamashita
Nobuhiko
N
Yui
Yuko
Y
Sugaya
Arihiro
A
Kano
Atsushi
A
Maruyama
Hidetaka
H
Akita
Rie
R
Ito
Kentaro
K
Kogure
Hideyoshi
H
Harashima
D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics; D011992:Endosomes / Q000378:metabolism; D008958:Models, Molecular; D010957:Plasmids / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry; D043862:Rotaxanes / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism*; D014162:Transfection / Q000379:methods*; D047391:alpha-Cyclodextrins / Q000008:administration & dosage / Q000737:chemistry
D043862:Rotaxanes; D047391:alpha-Cyclodextrins; D011092:Polyethylene Glycols; D004247:DNA