Copper peroxide-triggered reactive nitrogen effectively enhanced synergistic chemodynamic-immunotherapy

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Therapy

Background:

• Chemodynamic therapy (CDT) faces limitations due to short-lived reactive oxygen species (ROS) and poor bioavailability.
• Developing effective cancer treatments requires strategies to overcome these limitations and enhance therapeutic outcomes.

Purpose of the Study:

• To develop a synergistic strategy integrating CDT with immunotherapy.
• To engineer a multifunctional nanocarrier for enhanced tumor cell killing and immune response activation.

Main Methods:

• Fabrication of a multifunctional nanocarrier (HMSN-Met@HA-CuO₂) for co-delivery of metformin and CuO₂.
• Utilizing CuO₂ to amplify intracellular ROS generation and induce cuproptosis.
• Employing metformin (Met) to release nitric oxide (NO), which converts ROS to more stable reactive nitrogen species (RNS).

Main Results:

• The nanocarrier successfully generated ROS and induced cuproptosis.
• Conversion of ROS to RNS by NO led to sustained damage to lipids, proteins, and DNA.
• Demonstrated potent tumor cell cytotoxicity and activation of an antitumor immune response.
• Achieved significantly improved antitumor efficacy through the combined CDT and immunotherapy approach.

Conclusions:

• The developed nanocarrier system effectively converts oxygen radicals to nitrogen radicals.
• This strategy enhances the combinatorial application of CDT and immunotherapy for improved antitumor efficacy.
• Highlights the potential of ROS-to-RNS conversion in cancer therapy.