Biocleavable polyrotaxane-plasmid DNA polyplex for enhanced gene delivery

Tooru Ooya, Hak Soo Choi, Atsushi Yamashita, Nobuhiko Yui, Yuko Sugaya, Arihiro Kano, Atsushi Maruyama, Hidetaka Akita, Rie Ito, Kentaro Kogure, Hideyoshi Harashima

Research output: Contribution to journalArticlepeer-review

236 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3852-3853
Number of pages2
JournalJournal of the American Chemical Society
Volume128
Issue number12
DOIs
Publication statusPublished - Mar 29 2006

All Science Journal Classification (ASJC) codes

  • Chemistry(all)

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