Sulfur-Vacancy-Engineered Two-Dimensional Cu@SnS2–x Nanosheets Constructed via Heterovalent Substitution for High-Efficiency Piezocatalytic Tumor Therapy

Ultrasound (US)-mediated piezocatalytic tumor therapy has attracted much attention due to its notable tissue-penetration capabilities, noninvasiveness, and low oxygen dependency. Nevertheless, the efficiency of piezocatalytic therapy is limited due to an inadequate piezoelectric response, low separation of electron-hole (e^--h⁺) pairs, and complex tumor microenvironment (TME). Herein, an ultrathin two-dimensional (2D) sulfur-vacancy-engineered (S_v-engineered) Cu@SnS_2-x nanosheet (NS) with an enhanced piezoelectric effect was constructed via the heterovalent substitution strategy of Sn⁴⁺ by Cu²⁺. The introduction of Cu²⁺ ion not only causes changes in the crystal structure to increase polarization but also generates rich S_v to decrease band gap from 2.16 to 1.62 eV and inhibit e^--h⁺ pairs recombination, collectively leading to the highly efficient generation of reactive oxygen species under US irradiation. Moreover, Cu@SnS_2-x shows US-enhanced TME-responsive Fenton-like catalytic activity and glutathione depletion ability, further aggravating the oxidative stress. Both in vitro and in vivo results prove that the S_v-engineered Cu@SnS_2-x NSs can significantly kill tumor cells and achieve high-efficiency piezocatalytic tumor therapy in a biocompatible manner. Overall, this study provides a new avenue for sonocatalytic therapy and broadens the application of 2D piezoelectric materials.