H₂O₂ Self-Supplied Zinc Peroxide/Platinum Nanozyme For Tumor Catalytic Therapy

Nanozyme-mediated tumor catalytic therapy is a novel cancer treatment method,which uses the nanozyme with catalytic performance to convert hydrogen peroxide（H₂O₂）in tumor microenvironment（TME）into harmful hydroxyl radicals（·OH）,inducing tumor cell apoptosis or necrosis.Compared to traditional treatment,nanozyme-mediated catalytic therapy possesses higher tumor specificity.It can effectively kill tumor cells at low doses and reduce treatment side effects.However,the insufficient supply of endogenous H₂O₂in TME limits the catalytic efficiency of nanozyme.In addition,the complexity,diversity,and heterogeneity of tumor will limit the effectiveness of single catalytic therapy.To solve the problems,in this study,zinc peroxide（ZnO₂）was used as a nanocarrier,loaded with noble metal platinum nanoparticles（Pt NPs）with peroxidase（POD）-like activity,to construct an H₂O₂self-supplied zinc peroxide/platinum（ZnO₂@Pt）nanozyme for achieving tumor catalytic therapy.The in vitro experimental results showed that ZnO₂@Pt decomposed to produce H₂O₂and Zn²⁺under acidic TME,while Pt NPs exhibit the POD-like activity,catalyzing the production of·OH from H₂O₂.It provides conditions for the realization of tumor catalytic therapy.To evaluate the anti-tumor effect of ZnO₂@Pt in vivo,we constructed breast cancer-bearing mice model.The results showed that ZnO₂@Pt-mediated reactive oxygen species（ROS）generation strategy can effectively kill tumor cells.Meanwhile,Zn²⁺blocked the energy supply of tumor cell by inducing cellular mitochondrial dysfunction and inhibiting the production of ATP and NAD⁺.The synergistic effects of enzyme-like catalysis and ion interference energy metabolism prompted ZnO₂@Pt to effectively inhibit tumor growth in mice,achieving a tumor inhibition rate of 86.21%.In conclusion,this study constructed a multifunctional nanozyme based on acid TME-responsive ZnO₂,realized H₂O₂self-supplied nanozyme catalysis and ion interference energy metabolism therapy,and provided a new idea for the design of tumor specific nanozyme.