An Ultrasound-Activated Nanozyme Sonosensitizer for Photoacoustic Imaging-Guided Breast Cancer Sonodynamic and Starvation Combination Therapy

Sonodynamic therapy (SDT) is a promising ultrasound (US)-triggered therapeutic modality for anticancer treatments due to its high penetration, safety, and noninvasiveness. Its therapeutic efficiency is closely related to the performance of sonosensitizers and the oxygen concentration of the tumor microenvironment (TME). Herein, inspired by the adhesion of cocklebur, a rough-surface sonosensitizer gold platinum encapsulated with magnesium silicate loaded with glucose oxidase (AuPt@MgSiO₃@GOx, APMS-GOx) with an enzymatic cascade activity was designed to improve delivery capability, produce reactive oxygen species, and reduce the glucose concentration in tumor tissue. The rough surface of APMS-GOx can improve the ability of nanomaterials to deliver to tumor areas. The enzymatic cascade reaction of APMS-GOx can induce starvation therapy and improve the level of oxygen. Adequate oxygen can not only alleviate hypoxia TME but also further convert to singlet oxygen (¹O₂) by APMS-GOx under US activation. Moreover, the activity of GOx increases due to the involvement of US, resulting in a positive effect on starvation therapy. Furthermore, APMS-GOx exhibits near-infrared absorption properties, providing a photoacoustic imaging-guided combination breast tumor therapy strategy.