|Title:||Design, Synthesis and Evaluation of Cationic Polyn-Substituent Acrylamides for in Vitro Gene Delivery||Authors:||KE, JIN-HE
|Keywords:||Gene delivery;polycation||Issue Date:||2011||Source:||JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION||Journal Volume:||v.22||Journal Issue:||n.9||Start page/Pages:||1215-1236||Abstract:||
A series of polyN-substituent acrylamides PAms that differ in alkylamine side-chain was synthesized via free radical polymerization. The PAms were designed to examine the effects of the methylene numbers from 2 to 12 in the alkylamine side-chain on cytotoxicity, plasmid DNA pDNA binding affinity, cellular uptake efficiency and gene expression. The cytotoxicity of PAms evaluated in HEK293 cells using the MTT assay showed a trend of decreasing toxicity with increasing side-chain length and the IC50 values of all PAms were lower than that of polyethylenimine PEI control. The primary amine-based polymers were able to efficiently condense pDNA to form complexes with size ranging from 100 to 350 nm. The gene transfection ability of PAms is dominantly determined by the specific side-chain length that P8Am with an octylamine side-chain reveals higher gene expression than other PAms containing the same backbone structure. Although the gene transfection efficiency of PEI was better than all of PAms, PAms were found not to be uptake-limited. This was supported by the effect of chloroquine on transfection activity, based on the protease inhibition activity of chloroquine. Especially, complexes formed from P8Am displayed high uptake level relative to PEI, which was attributed to the proper structure of P8Am to compact pDNA to form stable nanoparticles in the heparin replacement assay. The present study offers the understanding to polymer structure that influences the transfection ability and gives useful information when designs efficient polymeric gene carrier.
|Appears in Collections:||醫學工程學研究所|
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.