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Reduction-Degradable Linear Cationic Polymers as Gene Carriers Prepared by Cu(I)-Catalyzed Azide-Alkyne Cycloaddition
Wang, Yang ; Zhang, Rui ; Xu, Ning ; Du, Fu-Sheng ; Wang, Ying-Li ; Tan, Ying-Xia ; Ji, Shou-Ping ; Liang, De-Hai ; Li, Zi-Chen
刊名biomacromolecules
2011
关键词CLICK CHEMISTRY IN-VITRO DNA DELIVERY FUNCTIONAL POLYMERS DISULFIDE LINKAGES POLY(AMIDO AMINE)S TERMINAL ALKYNES NUCLEIC-ACIDS POLYETHYLENIMINE TRANSFECTION
DOI10.1021/bm101005j
英文摘要Linear reduction-degradable cationic polymers with different secondary amine densities (S2 and S3) and their nonreducible counterparts (C2 and C3) were synthesized by Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) step-growth polymerization of the dialkyne-oligoamine monomers and the diazide monomers. These polymers were studied with a goal of developing a set of new gene carriers. The buffering capacity and DNA binding ability of these polymers were evaluated by acid base titration, gel retardation, and ethidium bromide (EB) exclusion assay. The polymers with lower amine density exhibit a weaker DNA-binding ability but a stronger buffering capacity in the range of pH 5.1 and 7.4. Particle size and zeta-potential measurements demonstrate that the polymers with higher amine density condense pDNA to form polyplexes with smaller sizes, while the disulfide bond in the backbone shows a negative effect on the condensing capability of the polymers, resulting in the formation of polyplexes with large size and nearly neutral surface. The reduction-sensitive polyplexes formed by polymer S2 of S3 can be disrupted by dithiothreitol (DTT) to release free DNA, which has been proven by the combination of gel retardation, EB exclusion assay, particles sizing, and zeta potential measurements. Cell viability measurements by MTT assay demonstrate that the reduction-degradable polymers (S2 and S3) have little cytotoxicity while the nonreducible polymers (C2 and C3) show obvious cytotoxicity, in particular, at high N/P ratios. In vitro transfection efficiencies of these polymers were evaluated using EGFP and luciferase plasmids as the reporter genes. Polymers S3 and S2 show much higher efficiencies than the nonreducible polymers C3 and C2 in the absence of 10% serum; unexpectedly, the lowest transfection efficiency has been observed for polymer S3 in the presence of serum.; Biochemistry & Molecular Biology; Chemistry, Organic; Polymer Science; SCI(E); EI; PubMed; 13; ARTICLE; 1; 66-74; 12
语种英语
内容类型期刊论文
源URL[http://ir.pku.edu.cn/handle/20.500.11897/150037]  
专题化学与分子工程学院
推荐引用方式
GB/T 7714
Wang, Yang,Zhang, Rui,Xu, Ning,et al. Reduction-Degradable Linear Cationic Polymers as Gene Carriers Prepared by Cu(I)-Catalyzed Azide-Alkyne Cycloaddition[J]. biomacromolecules,2011.
APA Wang, Yang.,Zhang, Rui.,Xu, Ning.,Du, Fu-Sheng.,Wang, Ying-Li.,...&Li, Zi-Chen.(2011).Reduction-Degradable Linear Cationic Polymers as Gene Carriers Prepared by Cu(I)-Catalyzed Azide-Alkyne Cycloaddition.biomacromolecules.
MLA Wang, Yang,et al."Reduction-Degradable Linear Cationic Polymers as Gene Carriers Prepared by Cu(I)-Catalyzed Azide-Alkyne Cycloaddition".biomacromolecules (2011).
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