TY - JOUR
T1 - Biocleavable polyrotaxane-plasmid DNA polyplex for enhanced gene delivery
AU - Ooya, Tooru
AU - Choi, Hak Soo
AU - Yamashita, Atsushi
AU - Yui, Nobuhiko
AU - Sugaya, Yuko
AU - Kano, Arihiro
AU - Maruyama, Atsushi
AU - Akita, Hidetaka
AU - Ito, Rie
AU - Kogure, Kentaro
AU - Harashima, Hideyoshi
PY - 2006/3/29
Y1 - 2006/3/29
N2 - A biocleavable polyrotaxane, having a necklace-like structure consisting of many cationic α-cyclodextrins (α-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 α-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 α-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.
AB - A biocleavable polyrotaxane, having a necklace-like structure consisting of many cationic α-cyclodextrins (α-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 α-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 α-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.
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U2 - 10.1021/ja055868+
DO - 10.1021/ja055868+
M3 - Article
C2 - 16551060
AN - SCOPUS:33645460372
SN - 0002-7863
VL - 128
SP - 3852
EP - 3853
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 12
ER -