title: Disulfide-containing brushed polyethylenimine derivative synthesized by click chemistry for nonviral gene delivery.
abstract: Polyaspartamide-based disulfide-containing brushed polyethylenimine derivatives P(Asp-Az)X-SS-PEIs were synthesized via click chemistry and evaluated as nonviral gene delivery carrier. First, azide-functional poly(aspartic acid) derivatives with various azide-group densities and monoalkyne-terminated PEI with disulfide linkages were synthesized. Then, click reaction between the azide-functional poly(aspartic acid) derivative as main chain and the monoalkyne-terminated PEI as branched chain resulted in high-molecular-weight disulfide-containing brushed PEI derivative. The structure of obtained polymers was confirmed by (1)H NMR and FTIR. It was shown that the disulfide-containing P(Asp-Az)X-SS-PEIs were able to bind plasmid DNA and condense DNA into small positive nanoparticles. The reduction-sensitivity of the P(Asp-Az)X-SS-PEI/DNA polyplexes was confirmed by gel retardation assay and dynamic light scattering (DLS) in the presence of DTT. In vitro experiments revealed that the reducible P(Asp-Az)X-SS-PEI not only had much lower cytotoxicity, but also posed high transfection activity (both in the presence and absence of serum) as compared to the control nondegradable 25 kDa PEI. This study indicates that a reducibly degradable brushed polymer P(Asp-Az)X-SS-PEI composed of low-molecular-weight (LMW) PEI via a disulfide-containing linkage can be a promising gene delivery carrier.
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education and Department of Chemistry, Wuhan University , Wuhan 430072, P.R. China.
authors.forename: Guangyan
authors.initials: G
authors.lastname: Zhang
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.forename: Qizhi
authors.initials: Q
authors.lastname: Yang
authors.forename: Renxi
authors.initials: R
authors.lastname: Zhuo
authors.forename: Xulin
authors.initials: X
authors.lastname: Jiang
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D057930:Click Chemistry; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics; D004220:Disulfides / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D057809:HEK293 Cells; D006801:Humans; D008156:Luciferases / Q000235:genetics; D010957:Plasmids / Q000008:administration & dosage* / Q000235:genetics; D011094:Polyethyleneimine / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D014162:Transfection
chemical_list: D004220:Disulfides; D011094:Polyethyleneimine; D004247:DNA; D008156:Luciferases