Nanoparticle mediated delivery of a GST inhibitor ethacrynic acid for sensitizing platinum based chemotherapy
Nanoparticle mediated delivery of a GST inhibitor ethacrynic acid for sensitizing platinum based chemotherapy
复制标题
纳米颗粒介导的 GST 抑制剂依他尼酸递送用于增敏铂类化疗
DOI：
10.1039/c4ra12040j
复制
发表时间：
2014-11
期刊：
影响因子：
3.9
通讯作者：
Jing, Xiabin
中科院分区：
文献类型：
--
作者：
Cai, Jing;Xie, Zhigang;Wang, Zehua;Jing, Xiabin
耐药性是铂类化疗的主要障碍，最常见的原因之一是 GSH 介导的解毒。为了克服这个问题，我们提出了GST抑制剂依他尼酸（EA）来减少GSH与铂类药物的结合，从而提高癌细胞对化疗的敏感性。我们构建了可生物降解的纳米颗粒来共同传递 EA 和 DACHPt（奥沙利铂的前体）。体外研究表明，混合纳米粒子在类细胞内环境中比在血液循环中更快地释放 EA 和 DACHPt，从而增强细胞 Pt 积累和 Pt-DNA 加合物形成。最重要的是，它表现出 EA 和 DACHPt 之间的协同作用，导致抗癌功效增强高达 4.6 倍。我们还在体内验证了这种方法，同时考虑到抗癌功效和全身毒性，纳米颗粒比游离药物的简单组合要好得多。结果表明，我们构建的纳米颗粒可能是克服癌症化疗中耐药问题的一种有前途的方法。
Drug resistance is a major obstacle for platinum based chemotherapy, and one of the most common reasons is GSH-mediated detoxification. To overcome this problem, we proposed ethacrynic acid (EA), a GST inhibitor, to reduce the conjugation of GSH with platinum agents so as to sensitize cancer cells to chemotherapy. We constructed biodegradable nanoparticles to co-deliver EA and DACHPt, a precursor of oxaliplatin. In vitro studies showed that the hybrid nanoparticles could release EA and DACHPt faster in intracellular-like environments than in blood circulation, enhancing the cellular Pt accumulation and Pt–DNA adduct formation. Most importantly, it showed a synergy effect between EA and DACHPt, resulting in an enhancement of up to 4.6 fold of the anticancer efficacy. We also verified this approach in vivo, taking into account both anticancer efficacy and systemic toxicity, and the nanoparticles were much better than the simple combination of free drugs. The results demonstrated that the nanoparticles we constructed could be a promising approach to overcome the drug resistant problem in cancer chemotherapy.
登录
查看更多内容
影响因子：
10.8
作者：
Qi, Ruogu;Liu, Shi;Jing, Xiabin
通讯作者：
Jing, Xiabin
影响因子：
9.7
作者：
Haihua Xiao;Dongfang Zhou;Shi Liu;Yonghui Zheng;Yubin Huang;X. Jing
通讯作者：
Haihua Xiao;Dongfang Zhou;Shi Liu;Yonghui Zheng;Yubin Huang;X. Jing
影响因子：
120.1
作者：
Rosen, H;Abribat, T
通讯作者：
Abribat, T
影响因子：
2.9
作者：
Bhattacharya C;Yu Z;Rishel MJ;Hecht SM
通讯作者：
Hecht SM
影响因子：
11.2
作者：
J. Ploemen;A. Schanke;B. V. Ommen;P. J. Bladeren
通讯作者：
J. Ploemen;A. Schanke;B. V. Ommen;P. J. Bladeren