Physiological respiration pressure-driven piezocatalytic therapy for malignant ascites with a gold-core magnified mesoporous piezoelectric nanoplatform.

Malignant ascites (MA), a life-threatening complication of advanced intra-abdominal cancers, poses a formidable clinical challenge due to its complex pathophysiology and the scarcity of effective, low-toxicity treatments. Here, we developed an intelligent respiratory pressure-responsive piezoelectric nanoplatform with a multilayer metal@mesoporous TiO2@mesoporous BaTiO3 architecture (MTB) for piezoelectric therapy of MA. By integrating a metal-TiO2 Schottky junction and a TiO2-BaTiO3 heterojunction into a mesoporous sandwich configuration, the nanoplatform achieves amplified polarization and suppressed charge recombination, thereby enabling efficient piezocatalytic activation driven by subtle intraperitoneal pressure oscillations from physiological diaphragmatic respiration. Systematic core screening identifies Au@mesoporous TiO2@mesoporous BaTiO3 (AuTB) as the optimal configuration, exhibiting superior piezoelectric responsiveness and reactive oxygen species (ROS) generation capability. Under the mild intra-abdominal pressure oscillations stimulation, AuTB efficiently produces ROS and induces immunogenic cell death (ICD) in tumor cells. In murine MA models, intraperitoneal administration of AuTB markedly suppresses tumor progression, reduces ascites accumulation, and significantly prolongs survival. Mechanistic studies reveal that AuTB-mediated piezocatalysis remodels the immunosuppressive microenvironment by promoting dendritic cell maturation, enhancing cytotoxic CD8+ T-cell activation, and reducing regulatory T cells and myeloid-derived suppressor cells. In conclusion, our work establishes a physiologically piezoelectric paradigm that converts endogenous respiratory mechanical energy into sustained antitumor activity, providing a promising translational nanotherapeutic strategy for MA.