Enzyme-MOF Nanoreactor Activates Nontoxic Paracetamol for Cancer Therapy

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Therapy

Background:

• Enzyme-prodrug cancer therapy offers improved selectivity and reduced toxicity compared to traditional chemotherapy.
• A major limitation is the short in vivo half-life of administered enzymes, hindering therapeutic efficacy.
• Developing persistent enzyme delivery systems is crucial for sustained therapeutic effects.

Purpose of the Study:

• To develop a novel nanoreactor system for sustained enzyme-prodrug activation in cancer cells.
• To investigate the efficacy of a tyrosinase-MOF nanoreactor in activating paracetamol for cancer therapy.
• To evaluate the long-lasting effects and mechanisms of action of the nanoreactor system.

Main Methods:

• Fabrication of a tyrosinase-metal-organic framework (MOF) nanoreactor.
• Internalization of the nanoreactor into cancer cells.
• Assessment of prodrug (paracetamol) activation and subsequent generation of reactive oxygen species (ROS).
• Measurement of glutathione (GSH) depletion and cancer cell death induction.

Main Results:

• Tyrosinase-MOF nanoreactors demonstrated sustained activation of paracetamol within cancer cells for up to three days.
• The activated prodrug generated cytotoxic reactive oxygen species (ROS) and depleted intracellular glutathione (GSH).
• Significant cell death was observed in drug-resistant cancer cells treated with nanoreactors and paracetamol, unlike free enzymes which lost activity rapidly.

Conclusions:

• Enzyme-MOF nanocomposites represent a persistent platform for enzyme-prodrug cancer therapy.
• This nanoreactor system overcomes the limitation of short enzyme half-lives, offering prolonged therapeutic effects.
• Tyrosinase-MOF nanoreactors show promise for developing novel, long-lasting cancer treatment strategies.