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 Zn²⁺ and PO₄^3- 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.