A Hydrogen-Releasing Nanozyme Engineers a Mitochondrial ROS Amplifier for Self-Sustaining Catalytic Immunotherapy

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Therapy

Background:

• Nanocatalytic therapy efficacy is limited by low hydrogen peroxide (H2O2) availability, nanozyme activity, and antioxidant scavenging.
• Accumulation of nanozymes at therapeutic concentrations is hindered by these factors.

Purpose of the Study:

• To develop a novel nanozyme (RhPd-H) that overcomes limitations in nanocatalytic therapy.
• To enhance peroxidase (POD)-mimetic activity and enable triggered hydrogen gas (H2) release for improved tumor treatment.

Main Methods:

• Development of a hydrogen-doped rhodium-palladium alloy (RhPd-H) nanozyme.
• Utilizing near-infrared (NIR) irradiation to trigger POD activity and H2 release.
• Investigating the dual-path reactive oxygen species (ROS) generation mechanism and in vivo tumor suppression.

Main Results:

• RhPd-H nanozyme demonstrated enhanced POD activity, producing hydroxyl radicals (·OH) and superoxide anion (·O2−).
• The nanozyme reprogrammed mitochondria to generate sustained ROS, leading to efficient tumor cell killing.
• In vivo studies showed long-term tumor retention, significant tumor growth suppression, and activation of antitumor immunity.

Conclusions:

• RhPd-H nanozyme establishes persistent oxidative stress by differentially regulating ROS, disrupting redox homeostasis.
• This metabolically amplified nanozyme therapy offers a novel approach beyond conventional catalytic therapy.
• The developed nanozyme shows potential for effective cancer treatment and immunotherapy activation.