卵巢癌细胞很容易对化疗药物产生耐受，这严重影响临床结果。开发新策略来增强化疗药物的靶向性，克服耐药性并最大程度地减少副作用，对于改善卵巢癌患者的临床结果具有重要意义。我们采用叶酸（FA）修饰的 ZIF-90 纳米材料（FA-ZIF- 90）通过双重靶向递送化疗药物顺铂（DDP），以改善其靶向性，特别是通过靶向线粒体来规避卵巢癌细胞中的顺铂耐药性。 FA-ZIF-90/DDP能够响应肿瘤细胞内酸度和ATP的双重刺激而快速释放DDP。FA-ZIF-90/DDP表现出良好的血液相容性。它被人卵巢癌顺铂耐药细胞 A2780/DDP 有效摄取并聚集在线粒体区域。 FA-ZIF-90/DDP显着抑制A2780/DDP细胞的线粒体活性和转移能力。此外，它还能有效诱导A2780/DDP细胞凋亡并克服顺铂耐药。体内实验表明，FA-ZIF-90/DDP可增加DDP在肿瘤组织中的积累，显着抑制肿瘤生长。FA修饰的ZIF-90纳米载体可提高化疗药物的肿瘤靶向性和抗肿瘤效果，降低毒副作用效果，并有望成为逆转卵巢癌耐药性的新治疗策略。© 2024 Xing 等人。

Ovarian cancer cells are prone to acquire tolerance to chemotherapeutic agents, which seriously affects clinical outcomes. The development of novel strategies to enhance the targeting of chemotherapeutic agents to overcome drug resistance and minimize side effects is significant for improving the clinical outcomes of ovarian cancer patients.We employed folic acid (FA)-modified ZIF-90 nanomaterials (FA-ZIF-90) to deliver the chemotherapeutic drug, cisplatin (DDP), via dual targeting to improve its targeting to circumvent cisplatin resistance in ovarian cancer cells, especially by targeting mitochondria. FA-ZIF-90/DDP could rapidly release DDP in response to dual stimulation of acidity and ATP in tumor cells.FA-ZIF-90/DDP showed good blood compatibility. It was efficiently taken up by human ovarian cancer cisplatin-resistant cells A2780/DDP and aggregated in the mitochondrial region. FA-ZIF-90/DDP significantly inhibited the mitochondrial activity and metastatic ability of A2780/DDP cells. In addition, it effectively induced apoptosis in A2780/DDP cells and overcame cisplatin resistance. In vivo experiments showed that FA-ZIF-90/DDP increased the accumulation of DDP in tumor tissues and significantly inhibited tumor growth.FA-modified ZIF-90 nanocarriers can improve the tumor targeting and anti-tumor effects of chemotherapeutic drugs, reduce toxic side effects, and are expected to be a novel therapeutic strategy to reverse drug resistance in ovarian cancer.© 2024 Xing et al.