title: Reduction biodegradable brushed PDMAEMA derivatives synthesized by atom transfer radical polymerization and click chemistry for gene delivery.
abstract: Novel reducible and degradable brushed poly(2-(dimethylamino) ethyl methacrylate) (PDMAEMA) derivatives were synthesized and evaluated as non-viral gene delivery vectors. First, alkyne-functionalized poly(aspartic acid) with a disulfide linker between the propargyl group and backbone poly([(propargyl carbamate)-cystamine]-α,β-aspartamide) (P(Asp-SS-AL)) was synthesized. Second, linear low molecular weight (LMW) monoazido-functionalized PDMAEMAs synthesized via atom transfer radical polymerization were conjugated to the polypeptide side-chains of P(Asp-SS-AL) via click chemistry to yield high molecular weight (HMW) polyaspartamide-based disulfide-containing brushed PDMAEMAs (PAPDEs). The PAPDEs were able to condense plasmid DNA to form 100 to 200nm polyplexes with positive ζ-potentials. Moreover, in the presence of dithiothreitol the PAPDEs degraded into LMW PDAMEMA, resulting in disintegration of the PAPDE/DNA polyplexes and subsequent release of plasmid DNA. In vitro experiments revealed that the PAPDEs were less cytotoxic and more effective in gene transfection than control 25kDa poly(ethyleneimine) and HMW linear PDMAEMA. In conclusion, reducible and degradable polycations composed of LMW PDMAEMAs coupled to a polypeptide backbone via reduction-sensitive disulfide bonds are effective gene vectors with an excellent cytocompatibility.
authors: Key Laboratory of Biomedical Polymers of the Ministry of Education, Department of Chemistry, Wuhan University, Wuhan 430072, People's Republic of China.
authors: Jia
authors: J
authors: Liu
authors: Yanglin
authors: Y
authors: Xu
authors: Qizhi
authors: Q
authors: Yang
authors: Cao
authors: C
authors: Li
authors: Wim E
authors: WE
authors: Hennink
authors: Renxi
authors: R
authors: Zhuo
authors: Xulin
authors: X
authors: Jiang
mesh_terms: D020341:Absorbable Implants; D057930:Click Chemistry / Q000379:methods; D004058:Diffusion; D004343:Drug Implants / Q000008:administration & dosage* / Q000138:chemical synthesis*; D057809:HEK293 Cells; D006801:Humans; D008422:Materials Testing; D008689:Methacrylates / Q000008:administration & dosage / Q000138:chemical synthesis*; D009757:Nylons / Q000138:chemical synthesis*; D010084:Oxidation-Reduction; D010957:Plasmids / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics*; D011108:Polymers / Q000138:chemical synthesis; D013499:Surface Properties; D014162:Transfection / Q000379:methods*
chemical_list: D004343:Drug Implants; D008689:Methacrylates; D009757:Nylons; D011108:Polymers; C407037:poly(2-(dimethylamino)ethyl methacrylate)