title: Pendant polymer:amino-β-cyclodextrin:siRNA guest:host nanoparticles as efficient vectors for gene silencing.
abstract: A novel siRNA delivery vector has been developed, based on the self-assembly of monosubstituted cationic β-CD derivatives with a poly(vinyl alcohol)MW27kD (PVA) main-chain polymer bearing poly(ethylene glycol)MW2000 (PEG) and acid-labile cholesterol-modified (Chol) grafts through an acid-sensitive benzylidene acetal linkage. These components were investigated for their ability to form nanoparticles with siRNA using two different assembly schemes, involving either precomplexation of the pendant Chol-PVA-PEG polymer with the cationic β-CD derivatives before siRNA condensation or siRNA condensation with the cationic β-CD derivatives prior to addition of Chol-PVA-PEG to engage host:guest complexation. The pendant polymer:amino-β-CD:siRNA complexes were shown to form nanoparticles in the size range of 120-170 nm, with a slightly negative zeta potential. Cell viability studies in CHO-GFP cells shows that these materials have 10(3)-fold lower cytotoxicities than 25 kD bPEI, while maintaining gene-silencing efficiencies that are comparable to those of benchmark transfection reagents such as bPEI and Lipofectamine 2000. These results suggest that the degradable Chol-PVA-PEG polymer is able to self-assemble in the presence of siRNA and cationic-β-CD to form nanoparticles that are an effective and low-toxicity vehicle for delivering siRNA cargo to target cells.
authors.affiliation: Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907, USA.
authors.forename: Aditya
authors.initials: A
authors.lastname: Kulkarni
authors.forename: Kyle
authors.initials: K
authors.lastname: DeFrees
authors.forename: Seok-Hee
authors.initials: SH
authors.lastname: Hyun
authors.forename: David H
authors.initials: DH
authors.lastname: Thompson
mesh_terms: D000818:Animals; D016466:CHO Cells; D002470:Cell Survival; D002784:Cholesterol / Q000031:analogs & derivatives / Q000737:chemistry; D006224:Cricetinae; D049452:Green Fluorescent Proteins / Q000235:genetics; D053758:Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D011142:Polyvinyl Alcohol / Q000737:chemistry; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D034741:RNA, Small Interfering; D047392:beta-Cyclodextrins; C095164:poly(oxyethylene) cholesteryl ether; D049452:Green Fluorescent Proteins; D011092:Polyethylene Glycols; D011142:Polyvinyl Alcohol; D002784:Cholesterol