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Drug Self‐Delivery Systems Based on Hyperbranched Polyprodrugs towards Tumor Therapy
Chemistry - An Asian Journal ( IF 3.5 ) Pub Date : 2018-03-24 , DOI: 10.1002/asia.201701697 Xiao Duan 1 , Jianxin Chen 1 , Yalan Wu 2 , Si Wu 3 , Dongyan Shao 1 , Jie Kong 1
Chemistry - An Asian Journal ( IF 3.5 ) Pub Date : 2018-03-24 , DOI: 10.1002/asia.201701697 Xiao Duan 1 , Jianxin Chen 1 , Yalan Wu 2 , Si Wu 3 , Dongyan Shao 1 , Jie Kong 1
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Amphiphilic hyperbranched polyprodrugs (DOX‐S‐S‐PEG) with drug repeat units in hydrophobic core linked by disulfide bonds were developed as drug self‐delivery systems for cancer therapy. The hydroxyl groups and the amine group in doxorubicin (DOX) were linked by 3,3′‐dithiodipropanoic acid as hydrophobic hyperbranched cores, then amino‐terminated polyethylene glycol monomethyl ether (mPEG‐NH2) as hydrophilic shell was linked to hydrophobic cores to form amphiphilic and glutathione (GSH)‐responsive micelle of hyperbranched polyprodrugs. The amphiphilic micelles can be disrupted under GSH (1 mg mL−1) circumstance. Cell viability of A549 cells and 293T cells was evaluated by CCK‐8 and Muse Annexin V & Dead Cell Kit. The disrupted polyprodrugs maintained drug activity for killing tumor cells. Meanwhile, the undisrupted polyprodrugs possessed low cytotoxicity to normal cells. The cell uptake experiments showed that the micelles of DOX‐S‐S‐PEG were taken up by A549 cells and distributed to cell nuclei. Thus, the drug self‐delivery systems with drug repeat units in hydrophobic cores linked by disulfide bonds showed significant special advantages: 1) facile one‐pot synthesis; 2) completely without toxic or non‐degradable polymers; 3) DOX itself functions as fluorescent labeled molecule and self‐delivery carrier; 4) drug with inactive form in hyperbranched cores and low cytotoxicity to normal cells. These advantages make them excellent drug self‐delivery systems for potential high efficient cancer therapy.
中文翻译：
基于超支化多前体药物的药物自我传递系统在肿瘤治疗中的应用
具有疏水性核心中通过二硫键连接的药物重复单元的两亲性超支化多前体药物（DOX‐S‐S‐PEG）被开发为用于癌症治疗的药物自我传递系统。阿霉素（DOX）中的羟基和胺基通过3,3'-二硫代二丙酸作为疏水性超支化核连接，然后将氨基端基的聚乙二醇单甲醚（mPEG-NH 2）作为亲水性壳与疏水性核连接。形成超支化前药的两亲和谷胱甘肽（GSH）响应胶束。两性胶束可在GSH（1 mg mL -1）情况。通过CCK-8和Muse Annexin V和Dead Cell Kit评估了A549细胞和293T细胞的细胞活力。被破坏的多前药维持杀死肿瘤细胞的药物活性。同时，未破坏的多前药对正常细胞具有低细胞毒性。细胞摄取实验表明，DOX-S-S-PEG的胶束被A549细胞吸收并分布到细胞核中。因此，具有通过二硫键连接的疏水核心中的药物重复单元的药物自我传递系统显示出显着的特殊优势：1）易于单罐合成；2）完全没有有毒或不可降解的聚合物；3）DOX本身起荧光标记分子和自送载体的作用；4）在超支化核心中具有非活性形式的药物，对正常细胞的细胞毒性低。
更新日期：2018-03-24
中文翻译：
基于超支化多前体药物的药物自我传递系统在肿瘤治疗中的应用
具有疏水性核心中通过二硫键连接的药物重复单元的两亲性超支化多前体药物（DOX‐S‐S‐PEG）被开发为用于癌症治疗的药物自我传递系统。阿霉素（DOX）中的羟基和胺基通过3,3'-二硫代二丙酸作为疏水性超支化核连接，然后将氨基端基的聚乙二醇单甲醚（mPEG-NH 2）作为亲水性壳与疏水性核连接。形成超支化前药的两亲和谷胱甘肽（GSH）响应胶束。两性胶束可在GSH（1 mg mL -1）情况。通过CCK-8和Muse Annexin V和Dead Cell Kit评估了A549细胞和293T细胞的细胞活力。被破坏的多前药维持杀死肿瘤细胞的药物活性。同时，未破坏的多前药对正常细胞具有低细胞毒性。细胞摄取实验表明，DOX-S-S-PEG的胶束被A549细胞吸收并分布到细胞核中。因此，具有通过二硫键连接的疏水核心中的药物重复单元的药物自我传递系统显示出显着的特殊优势：1）易于单罐合成；2）完全没有有毒或不可降解的聚合物；3）DOX本身起荧光标记分子和自送载体的作用；4）在超支化核心中具有非活性形式的药物，对正常细胞的细胞毒性低。
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