Mitochondria-targeting zeolitic imidazole frameworks to overcome platinum-resistant ovarian cancer

Abstract Epithelial ovarian cancer is still the leading cause of death in gynecology due to its resistance to platinum-based first-line chemotherapeutic drugs. The utilization of mitochondria-targeted drugs has become an important direction in anti-tumor drug research and development. In this work, cisplatin (DDP)-loaded ZIF-90 with mitochondrial-targeting was synthesized at room temperature with a high drug loading (11.7 %, calculated based on Pt content). The ZIF-90@DDP showed high cellular uptake and less toxicity in both non- and DDP-resistant ovarian cancer cells with effective pH- and ATP-responsive drug release. Both mitochondria-targeting and responsive drug release could increase the drug concentration in mitochondria of drug-resistant cancer cells to reverse such resistance. Conclusively, the mitochondria-targeting ZIF-90@DDP with high drug loading could trigger responsive drug release in mitochondria of epithelial ovarian cancer cells, inhibit DPP-resistant epithelial ovarian cancer cells, and reverse drug resistance.