Single Atom Catalysts Remodel Tumor Microenvironment for Augmented Sonodynamic Immunotherapy.

Area of Science:

• Nanotechnology
• Immunotherapy
• Materials Science

Background:

• The immunosuppressive tumor microenvironment (TME) hinders effective cancer immunotherapy.
• Sono-immunotherapy shows promise but is limited by TME factors like glutathione (GSH) and hypoxia.
• Overcoming these limitations is crucial for advancing sono-immunotherapy efficacy.

Purpose of the Study:

• To develop a new sono-immunotherapy strategy using palladium single-atom catalysts (SAC) to enhance sonodynamic responses.
• To remodel the immunosuppressive and sono-suppressive TME for improved therapeutic outcomes.
• To investigate the potential of SACs in boosting abscopal anti-tumor immune responses.

Main Methods:

• Construction of atomically dispersed Pd-C3 SACs (PdSA/Ti3-xC2Ty) using Ti3-xC2Ty nanosheets with rich Ti vacancies.
• Evaluation of sonodynamic effects and TME modulation compared to Pd nanoparticle-loaded counterparts.
• Assessment of immune responses, including dendritic cell maturation and macrophage polarization, in bilateral tumor models.

Main Results:

• PdSA/Ti3-xC2Ty exhibited augmented sonodynamic effects due to SAC-facilitated electron-hole separation.
• The strategy effectively depleted GSH and relieved hypoxia by utilizing ultrasound-excited holes and H2O2 decomposition.
• Sono-immunotherapy promoted anti-tumor immunity, leading to complete tumor eradication and regression of metastatic lesions.

Conclusions:

• Single-atom catalysts offer a potent strategy for sono-immunotherapy by effectively remodeling the TME.
• The developed PdSA/Ti3-xC2Ty system demonstrates significant potential for enhancing anti-tumor immune responses.
• This approach highlights a promising direction for overcoming immunotherapy resistance in cancer treatment.