Engineering sono-electro-enzymatic nanocouplers for PANoptosis-associated glioma therapy

Traditional piezoelectric cancer therapy primarily uses ultrasound to activate piezoelectric biomaterials to generate radicals for killing tumor cells. Although effective, this approach faces challenges including tumor resistance to oxidative stress and limited therapeutic efficacy of traditional piezoelectric biomaterials. In this work, we rationally design and engineer a single-phase sono-electro-enzymatic nanocoupler that intrinsically couples sono-piezoelectric conversion, charge-driven redox catalysis, and enzyme-mimetic bioactivity. This nanocoupler is engineered by strategically doping Mn into Aurivillius phase SrBi 4 Ti 4 O 15 nanosheets. The Mn doping simultaneously enhances the apparent local electromechanical response, reduces the apparent optical bandgap, and creates Mn 2+ /Mn 3+ redox centers that feature multienzyme-mimetic catalytic activities. Under ultrasound stimulation, piezoelectric activation is coupled with Mn-mediated catalytic redox reactions, forming an amplified sono-electro-enzymatic cascade. This cascade activates multiple PANoptosis-related cell-death pathways, effectively inducing tumor cell death. This work establishes a sono-electro-enzymatic cascade that induces a PANoptosis-like multimodal cell-death phenotype, providing a representative paradigm for piezoelectric catalysis-enabled suppression of postsurgical glioma recurrence.