Ultrasound-activated RuO₂ amplified oxidative stress therapy.

Area of Science:

• Biomaterials Science
• Nanomedicine
• Cancer Therapy

Background:

• Malignant tumors present limited therapeutic options due to a lack of molecular targets and a redox-adaptive tumor microenvironment.
• Overcoming tumor redox resistance is crucial for effective cancer treatment.

Purpose of the Study:

• To develop a ruthenium dioxide (RuO2) sonosensitizer for cascade-amplified oxidative stress therapy.
• To investigate the sonoelectric effect of RuO2 for enhanced reactive oxygen species (ROS) generation and antioxidant depletion.

Main Methods:

• Development of a RuO2 sonosensitizer.
• Ultrasound (US) stimulation to induce sonoelectric response and ROS generation.
• Assessment of intracellular ROS levels and glutathione (GSH) depletion.
• In vitro evaluation of cellular uptake, oxidative damage, and apoptosis.
• In vivo studies using photoacoustic imaging for tumor accumulation and efficacy assessment in tumor-bearing mice.

Main Results:

• RuO2 generated a sonoelectric response upon US stimulation, enhancing H2O2 decomposition and oxygen evolution.
• This led to excessive ROS production (˙OH, ˙O2-) and concurrent depletion of intracellular GSH, creating a self-reinforcing "ROS storm".
• RuO2 exhibited efficient cellular internalization, induced oxidative damage and apoptosis, and significantly suppressed tumor growth in vivo with favorable biocompatibility.

Conclusions:

• The developed RuO2 sonosensitizer provides a sonoelectric-enhanced platform for cancer therapy.
• This strategy effectively integrates ROS overproduction with antioxidant depletion to overcome tumor redox resistance.
• The findings offer a mechanistically advanced approach for improved therapeutic outcomes in malignant tumors.