title: Development of a low toxicity, effective pDNA vector based on noncovalent assembly of bioresponsive amino-β-cyclodextrin:adamantane-poly(vinyl alcohol)-poly(ethylene glycol) transfection complexes.
abstract: A host:guest-derived gene delivery vector has been developed, based on the self-assembly of cationic β-CD derivatives with a poly(vinyl alcohol) (MW 27 kDa) (PVA) main chain polymer bearing poly(ethylene glycol) (MW 750) (PEG) or MW 2000 PEG and acid-labile adamantane-modified (Ad) grafts through an acid-sensitive benzylidene acetal linkage. These components were investigated for their ability to promote supramolecular complex formation with pDNA using two different assembly schemes, involving either precomplexation of the pendent Ad-PVA-PEG polymer with the cationic β-CD derivatives before pDNA condensation (method A) or pDNA condensation with the cationic β-CD derivatives prior to addition of Ad-PVA-PEG to engage host:guest complexation (method B). The pendent polymers were observed to degrade under acidic conditions while remaining intact for more than 5 days at pH 7. HeLa cell culture data show that these materials have 10(3)-fold lower cytotoxicities than 25 kDa bPEI while maintaining transfection efficiencies that are superior to those observed for this benchmark cationic polymer transfection reagent when the method A assembly scheme is employed. These findings suggest that degradable cationic polymer constructs employing multivalent host:guest interactions may be an effective and low-toxicity vehicle for delivering nucleic acid cargo to target cells.
authors.affiliation: Departments of Chemistry and Biomedical Engineering, Purdue University , 560 Oval Drive, West Lafayette, Indiana 47907, United States.
authors.forename: Aditya
authors.initials: A
authors.lastname: Kulkarni
authors.forename: Wei
authors.initials: W
authors.lastname: Deng
authors.forename: Seok-hee
authors.initials: SH
authors.lastname: Hyun
authors.forename: David H
authors.initials: DH
authors.lastname: Thompson
mesh_terms: D000218:Adamantane / Q000737:chemistry / Q000633:toxicity; D000586:Amination; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000008:administration & dosage*; D006367:HeLa Cells; D006801:Humans; D010957:Plasmids / Q000008:administration & dosage*; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000633:toxicity; D011142:Polyvinyl Alcohol / Q000737:chemistry* / Q000633:toxicity; D014162:Transfection; D047392:beta-Cyclodextrins / Q000737:chemistry* / Q000633:toxicity
chemical_list: D047392:beta-Cyclodextrins; D011092:Polyethylene Glycols; D011142:Polyvinyl Alcohol; D004247:DNA; C031215:betadex; D000218:Adamantane