Sulfur-Vacancy-Engineered Two-Dimensional Cu@SnS 2- 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 Sn 4+ by Cu 2+ . The introduction of Cu 2+ 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.