Breaking the "Whack-a-Mole" Dilemma in Cancer Therapy: Ultrasound-Propelled ROS Storm Enables Triple-Modal Cell Death

Area of Science:

• Nanomedicine
• Cancer Therapy
• Regulated Cell Death (RCD)

Background:

• Apoptosis is a key cancer therapy, but ferroptosis and cuproptosis offer new dimensions.
• Conventional ferroptosis inducers face stability and drug resistance issues.
• Nanozymes present solutions due to catalytic activity and tumor microenvironment responsiveness.

Purpose of the Study:

• To design a sonodynamic single-atom copper nanozyme (CuSAE) overcoming monotherapy limitations.
• To implement a "pre-depletion and storm amplification" strategy for enhanced cancer treatment.
• To combat therapeutic resistance by synchronously activating multiple regulated cell death pathways.

Main Methods:

• Designed a sonodynamic single-atom copper nanozyme (CuSAE).
• Employed a "pre-depletion and storm amplification" strategy.
• Investigated CuSAE efficacy in mouse models of ovarian cancer.

Main Results:

• CuSAE generated a reactive oxygen species (ROS) storm to activate apoptosis, ferroptosis, and cuproptosis.
• Achieved remarkable tumor-killing efficacy and therapeutic outcomes in ovarian cancer models.
• Demonstrated CuSAE as a versatile platform enhancing anticancer effects.

Conclusions:

• The developed CuSAE nanozyme effectively combats therapeutic resistance.
• Simultaneous activation of ferroptosis and cuproptosis enhances anticancer effects.
• CuSAE offers a promising nanomedicine strategy for advanced cancer therapy.