Bioinspired Structure Regulation of Apyrase-Like Nanozyme with Intracellular-Generated H2O2 for Tumor Catalytic Therapy

Abstract

Adenosine triphosphate (ATP) is the major resource of energy supply in tumor activity. Therefore, improving ATP consumption efficiencies is a promising approach for cancer therapy. Herein, inspired by the H2O2-involved structure regulation effect during the catalysis of natural protein enzymes, we developed an artificial H2O2-driven ATP catalysis-promoting system, the Ce-based metal-organic framework (Ce-MOF), for catalytic cancer therapy. In the presence of H2O2, the hydrolysis ATP activity of Ce-MOF(H2O2) was enhanced by around 1.6 times. Taking advantage of the endogenous H2O2 in cancerous cells, catalytic hydrolysis for intracellular ATP of the Ce-MOF achieves the inhibition of cancerous cell growth, which involves damaged mitochondrial function and autophagy-associated cell death. Furthermore, in vivo studies suggest that the Ce-MOF has a good tumor inhibition effect. The artificial H2O2-driven ATP catalysis-promoting system not only demonstrates high catalytic ATP consumption efficiencies for cancer therapy but also highlights a bioinspired strategy to expedite nanozyme research in both design and applied sciences.