Bioactive Layered Double Hydroxides for Synergistic Sonodynamic/Cuproptosis Anticancer Therapy with Elicitation of the Immune Response

Sonodynamic therapy (SDT) has promising application prospects in tumor therapy. However, SDT does not eradicate metastatic tumors. Herein, Cu-substituted ZnAl ternary layered double hydroxide nanosheets (ZCA NSs) were developed as both sonosensitizers and copper nanocarriers for synergistic SDT/cuproptosis cancer therapy. An optimized electronic structure more conducive to the sonodynamic process was obtained from ZCA NSs via the Jahn–Teller effect induced by the introduction of Cu2+, and the synthesized ZCA NSs regulated the intricate tumor microenvironment (TME) by depleting endogenous glutathione (GSH) to amplify oxidative stress for further enhanced SDT performance. Furthermore, cuproptosis was evoked by…

• NN
  National Natural Science Foundation of China

  Awards: 52072253, 32301191, U20A20254
• MO
  Ministry of Science and Technology of the People's Republic of China

  Award: 2022YFB3804600
• CP
  China Postdoctoral Science Foundation

  Awards: 2023T160467, 2022M722324
• CI
  Collaborative Innovation Center of Suzhou Nano Science and Technology
• HE
  Higher Education Discipline Innovation Project
• NS
  Natural Science Foundation of Jiangsu Province for Distinguished Young Scholars

  Award: BK20211544