Degradable and Piezoelectric Hollow ZnO Heterostructures for Sonodynamic Therapy and Pro-Death Autophagy

Piezoelectric materials can generate charges and reactive oxygen species (ROS) under external force stimulation for ultrasound-induced sonodynamic therapy (SDT). However, their poor piezoelectricity, fast electron–hole pair recombination rate, and biological toxicity of piezoelectric materials limit the therapeutic effects of piezoelectric SDT. In this study, hollow ZnO (HZnO) nanospheres were synthesized by using a one-step method. The hollow structure facilitated the deformation of HZnO under stimulation by ultrasound mechanical force and increased the piezoelectric constant. Subsequently, black phosphorus quantum dots (BPQDs) and arginine-glycine-aspartic acid peptide (RGD)-poly(ethylene glycol) (PEG) were combined with HZnO to further enhance the piezoelectric effect by constructing heterojunctions and enable tumor-targeting ability. During treatment, HZnO-BPQDs-PEG could degrade in an acidic tumor microenvironment and release Zn 2+ and PO 4 3– ions to induce pro-death autophagy. The ROS produced by SDT also accelerated autophagy and promoted ferroptosis in cancer cells. This study demonstrates that HZnO-BPQDs-PEG has a strong piezoelectric SDT effect and can effectively induce autophagy in cancer cells, providing a new idea for the design and application of piezoelectric materials for tumor therapy.