Biodegradable Metal-Organic-Frameworks-Mediated Protein Delivery Enables Intracellular Cascade Biocatalysis and...

Area of Science:

• Biomaterials Science
• Nanotechnology
• Cancer Biology

Background:

• Pyroptosis, a regulated cell death, presents a promising avenue for cancer treatment.
• Current strategies for inducing pyroptosis in cancer cells suffer from low efficiency and selectivity.
• Targeted delivery systems are needed to overcome these limitations in cancer therapy.

Purpose of the Study:

• To develop a novel biodegradable metal-organic framework (MOF) system for the targeted intracellular delivery of glucose oxidase (GOx).
• To investigate the selective induction of cancer cell pyroptosis through cascade biocatalysis mediated by GOx@Cu MOF.
• To explore the potential of this MOF-based strategy for advanced cancer therapeutic development.

Main Methods:

• Self-assembly of Cu2+ and 4,4'-azobisbenzoic acid with GOx to form protein-encapsulated GOx@Cu MOF nanoparticles.
• Intracellular delivery of GOx@Cu MOF into cancer cells.
• Triggering MOF degradation and GOx release by tumor-cell-overexpressed NQO1.
• Intracellular cascade biocatalysis involving GOx, glucose, H2O2, and Cu+ to generate hydroxyl radicals.

Main Results:

• GOx@Cu MOF efficiently delivered GOx into cancer cells.
• Tumor-specific NQO1 triggered MOF degradation and GOx release, leading to intracellular H2O2 overproduction.
• Released Cu2+ promoted Fenton-like reactions, generating hydroxyl radicals that induced cancer cell pyroptosis.
• The strategy effectively inhibited tumor cell growth.

Conclusions:

• Biodegradable GOx@Cu MOF nanoparticles serve as an effective platform for intracellular protein delivery and cascade biocatalysis.
• This approach enables selective induction of cancer cell pyroptosis via NQO1-triggered intracellular reactions.
• Harnessing MOFs for protein delivery and intracellular biocatalysis offers a powerful strategy for developing advanced cancer therapeutics.