Development of a low toxicity, effective pDNA vector based on noncovalent assembly of bioresponsive amino-?-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 ?-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 ?-CD derivatives before pDNA condensation (method A) or pDNA condensation with the cationic ?-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.

SUBMITTER: Kulkarni A 

PROVIDER: S-EPMC3417082 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature