基于中性阳离子刷状嵌段共聚物的肿瘤靶向氧化还原响应性非病毒基因传递纳米载体。
Tumor-targeted redox-responsive nonviral gene delivery nanocarriers based on neutral-cationic brush block copolymers.
机构信息
CAS Key Laboratory of Soft Matter Chemistry, Hefei National Laboratory for Physical Sciences at the Microscale, Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei, Anhui, 230026, China.
出版信息
Macromol Rapid Commun. 2014 Feb;35(4):466-73. doi: 10.1002/marc.201300719. Epub 2013 Nov 27.
Novel neutral-cationic brush block copolymer, poly[oligo(ethylene glycol) monomethyl ether methacrylate-co-folic acid methacrylate]-b-poly[2-(2-(2-(2-bromo-2-methylpropanoyloxy)-ethyl) disulfanyl) ethyl methacrylate-g-2-dimethylaminoethyl methacrylate], P(OEGMA-co-FAMA)-b-P(BSSMA-g-PDMAEMA), is synthesized via consecutive controlled radical polymerizations. Containing disulfide linkages bridging backbone and side chains in the cationic brush block and cancer cell-targeting ligands (folic acid) in the neutral hydrophilic block, the diblock copolymer is employed as a tumor-targeted redox-responsive degradable nonviral gene delivery vector. P(OEGMA-co-FAMA)-b-P(BSSMA-g-PDMAEMA) brush block copolymers can condense plasmid DNA (pDNA) efficiently via the formation of electrostatic polyplex micelles. Under reductive milieu, pDNA can be released due to the cleavage of disulfide linkages and accordingly pDNA-binding cationic PDMAEMA side chains. In addition, the brush block copolymer exhibits low cytotoxicity and the corresponding polyplex micelles show relatively high gene transfection efficiency.
新型中性阳离子刷状嵌段共聚物，聚[聚（乙二醇）甲醚甲基丙烯酸酯-co-叶酸甲基丙烯酸酯]-b-聚[2-（2-（2-（2-溴-2-甲基丙酰氧基）-乙基）二硫基）乙基甲基丙烯酸酯-g-2-二甲氨基乙基甲基丙烯酸酯]，P（OEGMA-co-FAMA）-b-P（BSSMA-g-PDMAEMA），通过连续的可控自由基聚合合成。该阳离子刷状嵌段共聚物含有二硫键桥接主链和侧链，中性亲水嵌段含有癌细胞靶向配体（叶酸），作为肿瘤靶向氧化还原响应可降解非病毒基因传递载体。P（OEGMA-co-FAMA）-b-P（BSSMA-g-PDMAEMA）刷状嵌段共聚物可以通过静电聚电解质复合胶束的形成有效地浓缩质粒 DNA（pDNA）。在还原环境下，由于二硫键的断裂和相应的 pDNA 结合阳离子 PDMAEMA 侧链，pDNA 可以被释放。此外，刷状嵌段共聚物表现出低细胞毒性，相应的聚电解质复合胶束显示出相对较高的基因转染效率。
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