Platinum-based DNA-adducting agents are used extensively in the clinic for cancer chemotherapy. However, the anti-tumor efficacy of these drugs is severely limited by cisplatin resistance, and this can lead to the failure of chemotherapy. One of cisplatin resistance mechanisms is associated with overexpression of glutathione S-transferases (GSTs), which would accelerate the deactivation of cisplatin and decrease its antitumor efficiency. Nanoscale micelles encapsulating ethacraplatin, a conjugate of cisplatin and ethacrynic acid (an effective GSTs inhibitor), can enhance the accumulation of active cisplatin in cancer cells by inhibiting the activity of GSTs and circumventing deactivation of cisplatin. In vitro and in vivo results provide strong evidence that GSTs inhibitor-modified cisplatin prodrug combined with nanoparticle encapsulation favor high effective platinum accumulation, significantly enhanced antitumor efficacy against cisplatin-resistant cancer and decreased system toxicity. It is believed that these ethacraplatin-loaded micelles have the ability of overcoming resistance of cancers toward cisplatin and will improve the prospects for chemotherapy of cisplatin-resistant cancers in the near future.

中文翻译：

---

在体外和体内通过用依他克拉铂胶束抑制谷胱甘肽S-转移酶（GST）来克服对顺铂的耐药性

铂基DNA加成剂在临床上广泛用于癌症化学疗法。但是，这些药物的抗肿瘤功效受到顺铂耐药性的严重限制，这可能导致化疗失败。顺铂耐药机制之一与谷胱甘肽S-转移酶（GST）的过度表达有关，这会加速顺铂的失活并降低其抗肿瘤效率。纳米囊团包裹了依他克拉铂，一种顺铂和乙炔酸（一种有效的GSTs抑制剂）的结合物，可以通过抑制GST的活性和绕开顺铂的失活来增强癌细胞中活性顺铂的积累。体外和体内结果提供了有力的证据，表明GSTs抑制剂修饰的顺铂前药与纳米颗粒包封相结合有助于铂的高效积累，显着增强了对顺铂耐药性癌症的抗肿瘤功效，并降低了系统毒性。据信，这些装载有依他克拉铂的胶束具有克服癌症对顺铂的耐药性的能力，并且将在不久的将来改善化学疗法对顺铂耐药的癌症的前景。