A Cascade ROS Nanoamplifier for Enhanced Sono-Chemodynamic Therapy of Osteosarcoma

Area of Science:

• Biomedical Engineering
• Materials Science
• Oncology

Background:

• Reactive oxygen species (ROS) amplification is crucial for effective sonodynamic/chemodynamic therapy (SDT/CDT) in osteosarcoma.
• Current sonosensitizers and nanozymes exhibit limitations including low ROS production, poor stability, and unfavorable tumor microenvironments (TME).

Purpose of the Study:

• To develop a novel strategy for amplifying ROS yield by combining enhanced nanozyme activity with TME regulation for osteosarcoma treatment.
• To engineer a heterojunction nanoplatform using RuO2 nanozymes and Zr-based metal-organic frameworks (Zr-MOF) to improve SDT/CDT efficacy.

Main Methods:

• Fabrication of a RuO2@Zr-MOF heterojunction with bandgap matching to enhance electron-hole separation kinetics.
• Utilizing RuO2 nanozymes as auxiliary semiconductors to sensitize Zr-MOF, suppress electron-hole recombination, and boost multienzyme-mimic activity.
• Investigating the nanoplatform's ability to deplete glutathione (GSH) and alleviate tumor hypoxia.

Main Results:

• The RuO2@Zr-MOF heterojunction demonstrated enhanced sonodynamic and chemodynamic activities due to improved electron transfer efficiency.
• The nanoplatform achieved cascade amplification of ROS production by boosting SDT/CDT, depleting GSH, and alleviating tumor hypoxia.
• Intravenous injection of RuO2@Zr-MOF combined with ultrasound irradiation resulted in complete elimination of osteosarcoma tumors without recurrence.

Conclusions:

• RuO2@Zr-MOF heterojunctions offer a promising strategy for amplifying ROS production and enhancing osteosarcoma therapy.
• RuO2 nanozymes show potential as supplementary semiconductors for sensitizing sonosensitizers, providing new insights for heterojunction engineering.
• This approach presents a novel therapeutic platform for refractory osteosarcoma, highlighting the significance of synergistic TME regulation and enhanced nanozyme activity.