title: Poly(amidoamine)s with pendant primary amines and flexible backbone for enhanced nonviral gene delivery: transfection and intracellular trafficking.
abstract: We synthesized poly(amidoamine)s with pendant primary amines and flexible backbone (polymers 1-3) by Michael polyaddition of N-tert-butyloxycarbonyl (N-Boc) protected diamine to 1,6-Bis(acrylamido)hexane, followed by the deprotection of N-Boc under acidic conditions. The physicochemical properties of polymers 1-3, including buffer capacity, DNA-binding capacity, cytotoxicity, particle sizes, and zeta potentials of polycation/DNA complexes, were explored. All the three polymers possess high buffer capacity and excellent DNA-binding capacity. In vitro MTT assay revealed that these synthesized poly(amidoamine)s were less cytotoxic than commercial branched PEI (25 kDa). These poly(amidoamine)s with pendant primary amines and flexible backbone were evaluated as in vitro nonviral gene delivery vectors for 293T and COS-7 cells. All the three polymers exhibited high transfection efficiencies, which were even higher than branched PEI (25 kDa) at optimized conditions. Further evidences from confocal laser scanning microscope (CLSM) demonstrated that the high transfection efficiencies of polymers 1-3 were due to the efficient uptake and intracellular trafficking of plasmid DNA in the cells during the transfection.
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan 430072, People's Republic of China.
authors.forename: Wen-Ming
authors.initials: WM
authors.lastname: Liu
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.forename: Ya-Nan
authors.initials: YN
authors.lastname: Xue
authors.forename: Na
authors.initials: N
authors.lastname: Peng
authors.forename: Xi-Ming
authors.initials: XM
authors.lastname: Xia
authors.forename: Ren-Xi
authors.initials: RX
authors.lastname: Zhuo
authors.forename: Shi-Wen
authors.initials: SW
authors.lastname: Huang
mesh_terms: D000588:Amines / Q000737:chemistry*; D001692:Biological Transport; D002460:Cell Line; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D011073:Polyamines / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000588:Amines; C531249:Poly(amidoamine); D011073:Polyamines