Ultra-Small Iron-Based Nanoparticles with Mild Photothermal-Enhanced Cascade Enzyme-Mimic Reactions for Tumor Therapy

Chemodynamic therapy (CDT), which utilizes the catalytic reactions of nanoparticles to inhibit tumor growth, is a promising approach in cancer therapy. However, its efficacy is limited by insufficient hydrogen peroxide (H2O2) concentration in tumor microenvironments and unsatisfactory enzymatic catalytic activity. To overcome these limitations, ultra-small iron-based (USIB) nanoparticles with cascaded superoxide dismutase (SOD)-mimic and peroxidase (POD)-mimic activities have been engineered. USIB nanoparticles initiated by SOD-mimic activity to transform superoxide anions (O2·−) into H2O2, elevating H2O2 levels in the tumor microenvironment and subsequently utilizing POD-mimic activity to convert H2O2 into the more reactive ·OH, thereby achieving the destruction of tumor cells. In addition, USIB nanoparticles possess photothermal conversion capabilities, and their enzymatic activity can be significantly enhanced under mild laser irradiation. Therefore, by addressing the issues of insufficient substrate concentration and low enzymatic catalytic activity, the therapeutic efficiency of CDT has been improved. Our research integrates the cascade catalytic reactions of nanozymes with laser irradiation, effectively inhibiting tumor growth and exhibiting outstanding biosafety, demonstrating promising therapeutic potential.