Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, P. R. China.
School of Materials Science and Engineering, Changchun University of Science and Technology, Changchun 130022, P. R. China.
Biomater Sci. 2019 Sep 1;7(9):3898-3905. doi: 10.1039/c9bm00884e. Epub 2019 Jul 18.
To target a response to a high oxidative stress environment of inflammatory or tumor sites, various reactive oxygen species (ROS) sensitive polymers have been developed as drug delivery systems. In this study, a novel oxidation sensitive copolymer, phenylboronic acid pinacol ester-functionalized methoxyl poly(ethylene glycol)-block-poly(phthalic anhydride-alter-glycidyl propargyl ether) (mPEG-b-P(PA-alt-GPBAe)), was designed and synthesized by ring-opening alternating copolymerization (ROAP) and click reaction. The copolymers could self-assemble into micelles in aqueous solution with an average size of 20.3 ± 9.3 nm, and are able to load hydrophobic anticancer drug (doxorubicin, DOX) with a high encapsulation efficiency of 75.2%. Interestingly, the encapsulated drug showed accelerated release in the trigger of HO, or at low pH values. The copolymers have low cytotoxicity indicated by the 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay towards 4T1 cells, which showed cell viabilities of more than 80% with treatment of our copolymers at concentrations up to 0.5 mg mL. The effective uptake of the drug-loaded micelles by 4T1 cells was investigated by confocal laser scanning microscopy (CLSM) and flow cytometry (FCM) analysis. Finally, compared with free DOX, the DOX-loaded nanoparticles exhibited a better antitumor effect and had lower systemic toxicity in 4T1 tumor-bearing mice. Therefore, this new kind of copolymer acting as a stimuli-responsive nanocarrier should represent a promising therapeutic platform for cancer therapy.
为了靶向炎症或肿瘤部位的高氧化应激环境，已经开发了各种活性氧（ROS）敏感聚合物作为药物传递系统。在这项研究中，设计并合成了一种新型氧化敏感共聚物，苯硼酸频哪醇酯功能化甲氧基聚乙二醇-嵌段-聚（邻苯二甲酸酐-交替-缩水甘油丙炔醚）（mPEG-b-P（PA-alt-GPBAe）），通过开环交替共聚（ROAP）和点击反应。共聚物可以在水溶液中自组装成平均尺寸为 20.3 ± 9.3nm 的胶束，并且能够负载疏水性抗癌药物（阿霉素，DOX），包封效率高达 75.2%。有趣的是，在 HO 的触发或在低 pH 值下，封装的药物显示出加速释放。通过 3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四氮唑溴盐（MTT）测定法，共聚物对 4T1 细胞的细胞毒性较低，当共聚物浓度高达 0.5mg mL 时，细胞活力超过 80%。通过共聚焦激光扫描显微镜（CLSM）和流式细胞术（FCM）分析研究了载药胶束被 4T1 细胞的有效摄取。最后，与游离 DOX 相比，载 DOX 的纳米粒子在 4T1 荷瘤小鼠中表现出更好的抗肿瘤效果和更低的全身毒性。因此，这种作为刺激响应性纳米载体的新型共聚物应该代表癌症治疗的有前途的治疗平台。
