Synthesis and characterization of a new polymer-drug conjugate with pH-induced activity
Synthesis and characterization of a new polymer-drug conjugate with pH-induced activity
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DOI：
10.1016/j.polymer.2012.06.006
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发表时间：
2012-07-19
期刊：
影响因子：
4.6
通讯作者：
Liang, Mong
中科院分区：
文献类型：
--
作者：
Chang, Hui-Ping;Chen, Jian-Ying;Liang, Mong
通过甲基丙烯酸自由基共聚合成了一种定义明确、具有ph响应特性和靶向特异性的刺激响应型四聚物。N-（2-羟丙基）甲基丙烯酰胺、甲基丙烯酰甘酰基磺甲恶唑和N-（甲基丙烯酰）甘酰甘氨酸4-硝基苯基酯。采用核磁共振、红外光谱、紫外-可见吸收、透射电镜和凝胶渗透色谱等方法研究了四聚物的结构和性能。固相免疫分析实验证明，将马来酰亚胺连接剂掺入四聚物中有助于其与抗体片段结合。TEM图像显示，四聚物自组装成直径为50 ~ 150nm的球形胶束。改变溶液的pH值会导致不同程度的聚集，在pH 6.5-3.5之间，根据实体瘤的细胞外环境和内吞作用的相关特性做出反应。此外，荧光光谱显示临界胶束浓度（CMC）为1 mg/mL。在DMSO存在下，由于溶剂化和电离作用，该四聚物对大肠杆菌的抑菌活性显著增强，且随着pH值的降低，抑菌活性增强。(C) 2012 Elsevier Ltd.版权所有。
A well-defined, stimuli-responsive tetrapolymer with pH-responsive characteristics and targeting specificity has been synthesized by radical copolymerization of methacrylic acid. N-(2-hydroxypropyl)methacrylamide, methacryloyl glycylglycyl sulfamethoxazole, and N-(methacryloyl)glycylglycine 4-nitrophenyl ester. The structure and properties of tetrapolymer were investigated by NMR, FT-IR, UV-visible absorption, TEM and gel permeation chromatography. Incorporation of maleimide linker into tetrapolymer facilitates its conjugation with antibody fragments, as demonstrated by the solid-phase immunoassay experiments. The TEM image shows that tetrapolymer had self-assembled a spherical micelle with a diameter ranging from 50 to 150 nm. Altering the pH of the solution leads to a different extent of aggregation at pH 6.5-3.5, responding in accordance with the properties associated with the extracellular environment of solid tumors and endocytosis. Furthermore, fluorescence spectroscopy indicated a critical micelle concentration (CMC) of 1 mg/mL. Because of the solvation and ionization effects, the tetrapolymer showed considerably enhanced antibacterial activities against Escherichia coli in the presence of DMSO and the antibacterial activity increased with decreasing pH value. (C) 2012 Elsevier Ltd. All rights reserved.