title: Multi-armed cationic cyclodextrin:poly(ethylene glycol) polyrotaxanes as efficient gene silencing vectors.
abstract: A family of branched polyrotaxanes (bPRTx(+)), threaded with multiple cationic α-cyclodextrins (α-CDs) onto a multi-armed poly(ethylene glycol) (PEG) core, were synthesized and studied as gene silencing vectors. These bPRTx(+) formed stable, positively charged complexes with diameters of 150-250 nm at N/P ratios as low as 2.5. The bPRTx(+) materials were shown to have gene-silencing efficiencies comparable to those of Lipofectamine 2000 (L2k) and bPEI, while displaying similar toxicity profiles. The unique structure of these polyrotaxanes allows them to effectively condense and complex siRNA into nanoparticles at much lower N/P ratios than L2k or bPEI. These findings suggest that bPRTx(+) may be useful materials for gene therapy applications.
authors.affiliation: Purdue University, Department of Chemistry, 560 Oval Drive, West Lafayette, IN 47907, USA.
authors.forename: Aditya
authors.initials: A
authors.lastname: Kulkarni
authors.forename: Kyle
authors.initials: K
authors.lastname: DeFrees
authors.forename: Ryan A
authors.initials: RA
authors.lastname: Schuldt
authors.forename: Alexander
authors.initials: A
authors.lastname: Vlahu
authors.forename: Ross
authors.initials: R
authors.lastname: VerHeul
authors.forename: Seok-Hee
authors.initials: SH
authors.lastname: Hyun
authors.forename: Wei
authors.initials: W
authors.lastname: Deng
authors.forename: David H
authors.initials: DH
authors.lastname: Thompson
mesh_terms: D000818:Animals; D002412:Cations; D003505:Cyclodextrins / Q000737:chemistry*; D020868:Gene Silencing; D005822:Genetic Vectors / Q000235:genetics; D051379:Mice; D041681:NIH 3T3 Cells; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry*; D020442:Poloxamer / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics*; D043862:Rotaxanes / Q000737:chemistry*; D014162:Transfection / Q000379:methods*
chemical_list: D002412:Cations; D003505:Cyclodextrins; D053769:Nanocapsules; D034741:RNA, Small Interfering; D043862:Rotaxanes; C475673:polyrotaxane; D020442:Poloxamer; D011092:Polyethylene Glycols