Single Atom‐Doped Nanosonosensitizers for Mutually Optimized Sono/Chemo‐Nanodynamic Therapy of Triple Negative Breast Cancer

Sonodynamic therapy (SDT) represents a promising therapeutic modality for treating breast cancer, which relies on the generation of abundant reactive oxygen species (ROS) to induce oxidative stress damage. However, mutant breast cancers, especially triple-negative breast cancer (TNBC), have evolved to acquire specific antioxidant defense functions, significantly limiting the killing efficiency of SDT. Herein, the authors have engineered a distinct single copper atom-doped titanium dioxide (Cu/TiO2 ) nanosonosensitizer with highly catalytic and sonosensitive activities for synergistic chemodynamic and sonodynamic treatment of TNBC. The single-atom Cu is anchored on the most stable Ti vacancies of hollow TiO2 sonosensitizers, which not only substantially improved the catalytic activity of Cu-mediated Fenton-like reaction, but also considerably augmented the sonodynamic efficiency of TiO2 by facilitating the separation of electrons (e- ) and holes (h+ ). Both the in vitro and in vivo studies demonstrate that the engineered single atom-doped nanosonosensitizers effectively achieved the significantly inhibitory effect of TNBC, providing a therapeutic paradigm for non-invasive and safe tumor elimination through the mutual process of sono/chemo-nanodynamic therapy based on multifunctional single-atom nanosonosensitizers.