Single Atom Catalysts Remodel Tumor Microenvironment for Augmented Sonodynamic Immunotherapy

Adv Mater. 2024 Jun;36(25):e2313670. doi: 10.1002/adma.202313670. Epub 2024 Mar 20.

Abstract

The immunosuppressive tumor microenvironment (TME) is a huge hurdle in immunotherapy. Sono-immunotherapy is a new treatment modality that can reverse immunosuppressive TME, but the sonodynamic effects are compromised by overexpressed glutathione (GSH) and hypoxia in the TME. Herein, this work reports a new sono-immunotherapy strategy using Pdδ+ single atom catalysts to enhance positive sonodynamic responses to the immunosuppressive and sono-suppressive TME. To demonstrate this technique, this work employs rich and reductive Ti vacancies in Ti3-xC2Ty nanosheets to construct the atomically dispersed Pd-C3 single atom catalysts (SAC) with Pd content up to 2.5 wt% (PdSA/Ti3-xC2Ty). Compared with Pd nanoparticle loaded Ti3-xC2Ty, PdSA/Ti3-xC2Ty single-atom enzyme showed augmented sonodynamic effects that are ascribed to SAC facilitated electron-hole separation, rapid depletion of overexpressed GSH by ultrasound (US) excited holes, and catalytic decomposition of endogenous H2O2 for relieving hypoxia. Importantly, the sono-immunotherapy strategy can boost abscopal antitumor immune responses by driving maturation of dendritic cells and polarization of tumor-associated macrophages into the antitumoral M1 phenotype. Bilateral tumor models demonstrate the complete eradication of localized tumors and enhance metastatic regression. Th strategy highlights the potential of single-atom catalysts for robust sono-immunotherapy by remodeling the tumor microenvironment.

Keywords: MXene; SAzymes; immunotherapy; single‐atom‐catalyst; sonodynamic therapy.

MeSH terms

  • Animals
  • Catalysis
  • Cell Line, Tumor
  • Glutathione / chemistry
  • Glutathione / metabolism
  • Humans
  • Immunotherapy*
  • Mice
  • Palladium / chemistry
  • Titanium / chemistry
  • Tumor Microenvironment*
  • Ultrasonic Therapy / methods

Substances

  • Titanium
  • Palladium
  • Glutathione