Manganese oxide-modified bismuth oxychloride piezoelectric nanoplatform with multiple enzyme-like activities for cancer sonodynamic therapy

Sonodynamic therapy (SDT) is considered as a new-rising strategy for cancer therapeutics, but the inefficient production of reactive oxygen species (ROS) by current sonosensitizers seriously hinders its further applications. Herein, a piezoelectric nanoplatform is fabricated for enhancing SDT against cancer, in which manganese oxide (MnOx) with multiple enzyme-like activities is loaded on the surface of piezoelectric bismuth oxychloride nanosheets (BiOCl NSs) to form a heterojunction. When exposed to ultrasound (US) irradiation, piezotronic effect can remarkably promote the separation and transport of US-induced free charges, and further enhance ROS generation in SDT. Meanwhile, the nanoplatform shows multiple enzyme-like activities from MnOx, which can not only downregulate the intracellular glutathione (GSH) level, but also disintegrate endogenous hydrogen peroxide (H2O2) to generate oxygen (O2) and hydroxyl radicals (•OH). As a result, the anticancer nanoplatform substantially boosts ROS generation and reverses tumor hypoxia. Ultimately, it reveals remarkable biocompatibility and tumor suppression in a murine model of 4 T1 breast cancer under US irradiation. This work provides a feasible pathway for improving SDT using piezoelectric platforms.