Multicomponent metal-organic framework nanocomposites for tumor-responsive synergistic therapy

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Materials Science

Background:

• Targeted tumor therapy aims to selectively kill cancer cells using tumor microenvironment (TME)-responsive nanoplatforms.
• Metal-organic frameworks (MOFs) offer versatile platforms for drug delivery and therapy.
• Developing multi-component nanostructures with synergistic therapeutic effects is crucial for enhanced cancer treatment.

Purpose of the Study:

• To develop a multi-component MOF nanocomposite (ZIF@GOx@PBNPs) for targeted tumor therapy.
• To investigate the cascade catalytic activity of the nanoplatform within the TME for synergistic starvation and chemodynamic therapy.
• To evaluate the in vitro and in vivo antitumor efficiency and specificity of the ZIF@GOx@PBNPs.

Main Methods:

• Fabrication of nanosized zeolitic imidazolate framework-8 (ZIF-8) encapsulating glucose oxidase (GOx) and Prussian blue nanoparticles (PBNPs).
• Assessment of cascade catalytic reactions triggered by TME conditions (weak acidity and glucose).
• Evaluation of starvation therapy via glucose consumption and chemodynamic therapy via Fenton reaction-like process.
• In vitro and in vivo studies to determine tumor inhibition and specificity.

Main Results:

• ZIF@GOx@PBNPs demonstrated sequential release and cascade catalytic activity in the TME.
• GOx initiated starvation therapy by consuming glucose and producing H2O2.
• PBNPs, released in acidic conditions, converted H2O2 into harmful radicals, enhancing oxidative damage.
• Significant tumor growth inhibition was observed in vitro and in vivo with minimal side effects.

Conclusions:

• The ZIF@GOx@PBNPs nanoplatform effectively utilizes TME-responsive cascade catalysis for synergistic starvation and chemodynamic therapy.
• This approach enhances reactive oxygen species production and selectively targets cancer cells.
• The nanoplatform shows promise as a therapeutic strategy with high efficiency and reduced side effects for targeted tumor treatment.