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

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Epithelial ovarian cancer (EOC) remains a leading cause of gynecological cancer mortality.
• Drug resistance to platinum-based chemotherapy is a major clinical challenge in EOC treatment.
• Mitochondria-targeted drug delivery offers a promising strategy to enhance anti-cancer efficacy.

Purpose of the Study:

• To synthesize and characterize cisplatin (DDP)-loaded ZIF-90 nanoparticles for mitochondria-targeted delivery.
• To evaluate the efficacy of ZIF-90@DDP in overcoming DDP resistance in epithelial ovarian cancer cells.
• To investigate the pH- and ATP-responsive drug release mechanism and its impact on drug-resistant cells.

Main Methods:

• Room temperature synthesis of ZIF-90 nanoparticles encapsulating cisplatin.
• High-throughput screening of drug loading capacity and characterization of ZIF-90@DDP.
• In vitro assessment of cellular uptake, cytotoxicity, and drug release in DDP-sensitive and DDP-resistant ovarian cancer cells.
• Evaluation of mitochondria-targeting efficiency and drug resistance reversal.

Main Results:

• Successfully synthesized ZIF-90@DDP with a high drug loading of 11.7% (Pt content).
• Demonstrated enhanced cellular uptake and reduced toxicity in both non- and DDP-resistant ovarian cancer cells.
• Observed effective pH- and ATP-responsive cisplatin release from ZIF-90@DDP.
• Confirmed that mitochondria-targeting and responsive release increased intracellular drug concentration, reversing DDP resistance.

Conclusions:

• Mitochondria-targeting ZIF-90@DDP nanoparticles exhibit high drug loading and trigger responsive drug release within ovarian cancer cells.
• This novel nanodrug delivery system effectively inhibits DDP-resistant epithelial ovarian cancer cells.
• ZIF-90@DDP holds significant potential for reversing drug resistance and improving therapeutic outcomes in ovarian cancer.