Zinc-Based ROS Amplifiers Trigger Cancer Chemodynamic/Ion Interference Therapy Through Self-Cascade Catalysis

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Nanozyme-mediated chemodynamic therapy shows promise for cancer treatment.
• Low hydrogen peroxide (H2O2) levels in the tumor microenvironment (TME) limit therapeutic efficacy.

Purpose of the Study:

• To develop an H2O2 self-supplying nanozyme for improved cancer therapy.
• To investigate the synergistic effects of chemodynamic therapy and ion interference therapy.

Main Methods:

• Constructed ZnO2@Pt nanozyme by loading platinum nanoparticles (Pt NPs) onto zinc peroxide (ZnO2).
• Investigated TME responsiveness, H2O2 self-supply, ROS amplification, and ion interference capabilities.
• Evaluated in vitro effects on cancer cells (ROS generation, ATP/NAD+ levels) and in vivo anticancer efficacy.

Main Results:

• ZnO2@Pt releases H2O2 in acidic TME and Pt NPs catalyze ROS generation.
• The nanozyme amplifies ROS via self-cascade catalysis and releases Zn2+ for ion interference.
• In vitro studies showed increased oxidative stress and reduced ATP/NAD+ levels.
• In vivo studies demonstrated significant tumor growth inhibition (89.7%) via ROS generation and metabolic pathway disruption.

Conclusions:

• Developed a TME-responsive nanozyme (ZnO2@Pt) for self-supplying H2O2 and ion interference therapy.
• The nanozyme effectively synergizes chemodynamic and ion interference therapies for enhanced anticancer effects.
• Presents a new strategy for designing tumor-specific nanozymes.