|Title:||Imidazole/Poly(Ethylene Glycol)-Substituted Poly(N-(8-Aminooctyl) Acrylamide) as Biocompatible and Efficient Gene Carrier||Authors:||KE, JIN-HE
|Keywords:||Non-viral gene carrier;chemical modification;imidazole;poly(ethylene glycol)||Issue Date:||2011||Source:||Journal of Biomaterials Science Polymer Edition||Start page/Pages:||1753-1775||Abstract:||
A novel cationic polymer was developed by conjugating imidazole and poly( ethylene glycol) (PEG) on poly(N-(8- aminooctyl)acrylamide) (P8Am) for complexing with pDNA to exhibit high gene expression with low cytotoxicity and the resistance against erythrocyte agglutination and serum inhibition . Cytotoxicity results indicated that these P8Am derivatives with varying substitutions were more biocompatible than unmodified P8Am and PEI control . Moreover , the particle size and zeta potential experiment demonstrated that they were capable of complexing pDNA into sub-micrometer (135-625 nm) and positively charged (+10 to + 43 mV) particles, while the high degree of substitution might impede their pDNA complexation ability that formed less positive and larger polyplexes. Flow cytometry analysis demonstrated that the cellular uptake efficiency was dependent on the degree of substitution; low degree of substitution would mediate high uptake efficiency. The gene- transfection ability, evaluated by luciferase assay, revealed low substitution in P8Am-IM11 (substituted with 11 mol% imidazole moieties) and P8Am-PG7 (substituted with 7 mol% PEG moieties) in transfected cells more efficient than unmodified P8Am. Therefore, a multi -functional P8Am derivative, P8Am-IM11-PG7, containing both imidazole and PEG , was developed according to the optimized contents. In the presence of serum, P8Am-IM11-PG7 polyplexes significantly enhanced the gene- transfection efficiency relative to unmodified P8Am polyplexes. Moreover, they exhibited minimal cytotoxicity and the erythrocyte aggregation assay showed that P8Am-IM11-PG7 polyplexes had good blood compatibility as compared to P8Am and PEI polyplexes. This indicated that, by chemical modification, P8Am-IM11-PG7 could possess the required abilities to overcome the difficulties encountered in gene transfection and be a promising alternative of a gene carrier.
|Appears in Collections:||醫學工程學研究所|
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