title: Bioreducible poly(amido amine)s with oligoamine side chains: synthesis, characterization, and structural effects on gene delivery.
abstract: A group of bioreducible poly(amido amine)s containing multiple disulfide linkages in main chain and oligoamines in side chain (SS-PAOAs) were prepared by Michael-type polyaddition of N-tert-butyloxycarbonyl (N-Boc) protected oligoamine to the disulfide-containing cystaminebisacrylamide, followed by deprotection of the Boc-protective groups. These linear polymers show strong DNA condensation capability at low N/P ratios. The chemical structure of oligoamine side chains (i.e. amine type and amino spacer length) in the SS-PAOAs has a distinct effect on their buffer capacity, transfection efficiency and toxicity profile. The SS-PAOAs containing secondary amino functions in the side chain show high buffer capacities and are able to transfect COS-7 cells in vitro at low N/P ratios, with transfection efficiencies similar or even higher than those of 25 kDa branched pEI, along with very low cytotoxicity as determined by XTT assay. Increase of the alkyl spacer from ethylene to propylene between the amino units in side chains results in significant lower transfection and increased toxicity. This study presents detailed factors influencing the relationship between structure and gene delivery properties and may provide helpful insights for the further development of safe and efficient non-viral vectors.
authors.affiliation: Department of Biomedical Chemistry, Institute for Biomedical Technology (BMTI), Faculty of Science and Technology, University of Twente, P.O. Box 217, 7500 AE Enschede, The Netherlands.
authors.forename: Chao
authors.initials: C
authors.lastname: Lin
authors.forename: Cees-Jan
authors.initials: CJ
authors.lastname: Blaauboer
authors.forename: Miguel Mateos
authors.initials: MM
authors.lastname: Timoneda
authors.forename: Martin C
authors.initials: MC
authors.lastname: Lok
authors.forename: Mies
authors.initials: M
authors.lastname: van Steenbergen
authors.forename: Wim E
authors.initials: WE
authors.lastname: Hennink
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Zhong
authors.forename: Jan
authors.initials: J
authors.lastname: Feijen
authors.forename: Johan F J
authors.initials: JF
authors.lastname: Engbersen
mesh_terms: D000818:Animals; D019556:COS Cells; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002522:Chlorocebus aethiops; D018014:Gene Transfer Techniques; D009757:Nylons / Q000737:chemistry* / Q000494:pharmacology; D011073:Polyamines / Q000008:administration & dosage / Q000737:chemistry*
chemical_list: D009757:Nylons; D011073:Polyamines