title: Cationic α-cyclodextrin:poly(ethylene glycol) polyrotaxanes for siRNA delivery.
abstract: RNA interference has broad therapeutic potential due to its high specificity and ability to potentially evade drug resistance. Three cationic α-cyclodextrin:poly(ethylene glycol) polyrotaxanes derived from polymer axles of different sizes (MW 2,000, 3,400, and 10,000) have been synthesized for delivering siRNA. These polyrotaxanes are able to condense siRNA into positively charged particles that are <200 nm in diameter, enabling their facile internalization into mammalian cells. The cationic polyrotaxanes display cytotoxicity profiles that are >10(2)-fold lower than the commercial standard bPEI and gene silencing efficiencies that are comparable to those of both Lipofectamine 2000 and bPEI. Our findings suggest that the cationic polyrotaxanes display a size-activity relationship, wherein the higher molecular weight polyrotaxanes (PEG3,400 and 10,000) are able to condense and deliver siRNA better than the lower molecular weight material (PEG2,000).
authors: Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907, USA.
authors: Aditya
authors: A
authors: Kulkarni
authors: Kyle
authors: K
authors: DeFrees
authors: Ryan A
authors: RA
authors: Schuldt
authors: Seok-Hee
authors: SH
authors: Hyun
authors: Kyle J
authors: KJ
authors: Wright
authors: Charu K
authors: CK
authors: Yerneni
authors: Ross
authors: R
authors: VerHeul
authors: David H
authors: DH
authors: Thompson
mesh_terms: D000818:Animals; D016466:CHO Cells; D002412:Cations; D006224:Cricetinae; D003412:Cricetulus; D003505:Cyclodextrins / Q000737:chemistry; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008055:Lipids / Q000737:chemistry; D051379:Mice; D018625:Microscopy, Atomic Force; D008970:Molecular Weight; D041681:NIH 3T3 Cells; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D043862:Rotaxanes / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry; D047391:alpha-Cyclodextrins / Q000737:chemistry*
chemical_list: D002412:Cations; D003505:Cyclodextrins; D008055:Lipids; C086724:Lipofectamine; D034741:RNA, Small Interfering; D043862:Rotaxanes; D012997:Solvents; D047391:alpha-Cyclodextrins; D049452:Green Fluorescent Proteins; D011092:Polyethylene Glycols; C032613:alpha-cyclodextrin
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