pH-sensitive amphiphilic copolymer brush Chol-g-P(HEMA-co-DEAEMA)-b-PPEGMA: synthesis and self-assembled micelles for controlled anti-cancer drug release
pH-sensitive amphiphilic copolymer brush Chol-g-P(HEMA-co-DEAEMA)-b-PPEGMA: synthesis and self-assembled micelles for controlled anti-cancer drug release
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DOI：
10.1039/c4ra06413e
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发表时间：
2014-09
期刊：
影响因子：
3.9
通讯作者：
C. Zhang;Wensheng Wu;Na Yao;Bin Zhao;Lijuan Zhang
中科院分区：
文献类型：
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作者：
C. Zhang;Wensheng Wu;Na Yao;Bin Zhao;Lijuan Zhang
典型的胆固醇改性的两亲性共聚物聚（（羟乙基甲基丙烯酸酯）-co-甲基丙烯酸二乙氨基乙酯（聚乙二醇甲基醚甲基丙烯酸酯）（Chol-g-P（HEMA-co-DEAEMA）-b-PPEGMA），具有特定的pH敏感/亲水/疏水结构，含有不同比例的pH-通过电子转移原子转移自由基再生活化剂的组合，设计并合成了敏感的PDEAEMA片段聚合（ARGET ATRP）和醇解反应，其自组装的三层胶束被用作阿霉素（DOX）的递送载体。聚合物的结构用1H NMR和GPC进行了表征。通过荧光光谱法确认了聚合物在不同pH值下的临界胶束浓度（CMC），即使在弱酸性条件（pH 6.0）下，两种聚合物的CMC也分别为9.33 mg L-1和13.18 mg L-1。研究了聚合物在不同pH值溶液中的pKb值、粒径和zeta电位，考察了聚合物的pH敏感性。通过透射电子显微镜（TEM）检测聚合物的形态形状。随着pH值的降低，聚合物胶束的粒径和zeta电位显著增大。通过透析法将DOX负载到胶束中，与两种聚合物的pH 7.4相比，当溶液pH为6.0时，体外释放速率急剧增加。测定了对HepG 2细胞的细胞毒性作用，并与游离DOX进行了比较，分别导致聚合物和DOX负载胶束的低细胞毒性和高细胞毒性。这些结果表明，pH敏感胶束可作为潜在的抗癌药物载体。
Typical cholesterol modified amphiphilic copolymers poly((hydroxyethyl methylacrylate)-co-(2-(diethylamino)ethyl methacrylate))-b-poly(poly(ethylene glycol) methyl ether methacrylate) (Chol-g-P(HEMA-co-DEAEMA)-b-PPEGMA) with specific pH-sensitive/hydrophilic/hydrophobic structures containing different ratios of pH-sensitive PDEAEMA segments were designed and synthesized via the combination of activators regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP) and alcoholysis reaction, and their self-assembled three-layered micelles were used as doxorubicin (DOX) delivery carriers. The structures of the polymers were determined by 1H NMR and GPC. The critical micelle concentrations (CMC) of the polymers at different pH values were confirmed by fluorescence spectroscopy, resulting in 9.33 mg L−1 and 13.18 mg L−1 for two polymers even at weakly acidic conditions (pH 6.0). The pKb values, particle sizes and zeta potentials of the polymers in the solutions with different pH values were studied in order to investigate the pH-sensitivity of the polymers. The morphological shapes of the polymers were detected by transmission electron microscopy (TEM). As the pH decreased, the sizes and zeta potentials of the polymeric micelles increased markedly. DOX was loaded in the micelles by the dialysis method, and the in vitro release rate was enhanced sharply with the solution pH of 6.0 when compared to pH of 7.4 for both of the polymers. The cytotoxic effects for HepG2 cells were measured and compared with free DOX, resulting in low and high cytotoxicity for polymers and DOX-loaded micelles, respectively. All the results demonstrated that these pH-sensitive micelles could be used as the potential anti-cancer drug carriers.