Synergistic Anti-Cancer Therapy Through Ultrasound-Induced Piezocatalytic Therapy and Tumor Treatment Fields

The integration of therapeutic modalities to enhance cancer treatment efficacy and improve patient outcomes offers remarkable benefits over monotherapies and has attracted considerable attention. Herein, a synergistic anti-cancer therapy leveraging the benefits of physical tumor treating fields (TTFs) and dynamic piezocatalytic therapy (PCT) is presented, aiming to offer an optimized scheme while minimizing systemic side effects. First, a wearable ultrasound-induced wireless energy harvester based on biocompatible lead-free potassium sodium niobate-based piezocomposites is developed to enable efficient acoustic-to-electric conversion. The flexible printed circuit board architecture with two pairs of half-ring electrodes not only generates wide-anging alternating electric fields but also facilitates easy fixation and wearability. Second, biocompatible piezoelectric nanoparticles (NPs) serve as the piezocatalysts to promote the generation of reactive oxygen species (ROS) and to directly interfere with biological processes. Finally, in vivo evaluations using mouse models demonstrate that the combination of ultrasound-activated PCT and TTFs significantly inhibits tumor growth and modulates the tumor immune microenvironment. Notably, prominent synergistic antitumor effects are also observed in patient-derived xenograft (PDX) models of head and neck squamous cell carcinoma (HNSCC), highlighting a versatile approach to advance cancer treatment.