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

Colloids Surf B Biointerfaces. 2020 May:189:110837. doi: 10.1016/j.colsurfb.2020.110837. Epub 2020 Jan 30.

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.

Keywords: A2780 cells; Drug resistance; Ovarian cancer; Proliferation; ZIF - 90.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cisplatin / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Carriers / chemical synthesis
  • Drug Carriers / chemistry
  • Drug Carriers / pharmacology
  • Drug Liberation
  • Drug Resistance, Neoplasm / drug effects*
  • Drug Screening Assays, Antitumor
  • Female
  • Humans
  • Imidazoles / chemical synthesis
  • Imidazoles / chemistry
  • Imidazoles / pharmacology*
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Molecular Structure
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Particle Size
  • Structure-Activity Relationship
  • Surface Properties
  • Tumor Cells, Cultured
  • Zeolites / chemical synthesis
  • Zeolites / chemistry
  • Zeolites / pharmacology*

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Imidazoles
  • Zeolites
  • Cisplatin