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/TiO(2)) 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 TiO(2) sonosensitizers, which not only substantially improved the catalytic activity of Cu‐mediated Fenton‐like reaction, but also considerably augmented the sonodynamic efficiency of TiO(2) 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.