Biodegradable polymer-platinum drug conjugates to overcome platinum drug resistance
Biodegradable polymer-platinum drug conjugates to overcome platinum drug resistance
复制标题
可生物降解的聚合物-铂药物缀合物克服铂耐药性
DOI：
10.1039/c5ra11297d
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发表时间：
2015-01-01
期刊：
影响因子：
3.9
通讯作者：
Wang, Zehua
中科院分区：
文献类型：
--
作者：
Yang, Qiang;Qi, Ruogu;Wang, Zehua
耐药性和严重的剂量依赖性副作用是铂类药物进一步使用的主要障碍。两个公认的耐药机制是铂类药物的细胞内积累减少和硫结合解毒作用增加。聚合物-药物缀合物方法可以显着增强癌细胞对物质的摄取，因此可以以较低的剂量获得更好的抗癌效果，从而减少剂量依赖性副作用。在这里，我们合成了一种含有侧链 1,2-二齿羧基的可生物降解聚合物来螯合铂，而不引入硫原子来潜在地使铂药物解毒。聚合物-铂缀合物形成的纳米胶束显示出显着增加的细胞内积累，并且可以部分克服卵巢癌细胞的耐药性。
Drug resistance and severe dose-dependent side effects are the major obstacles to the further use of platinum agents. Two well-acknowledged mechanisms of resistance are the decreased intracellular accumulation and the increased sulfur-binding-detoxification of platinum agents. The polymer-drug conjugate approach can remarkably enhance the uptake of substances by cancer cells, therefore can achieve better anticancer effects with lower dosage, and thus reduce the dose-dependent side effects. Here we synthesized a biodegradable polymer containing pendant 1,2-bidentate carboxyl groups to chelate platinum without introducing sulfur atoms to potentially detoxify the platinum drugs. The polymer-platinum conjugate formed nanomicelles showed significantly increased intracellular accumulation and could partially overcome drug resistance in ovarian cancer cells.