Ultrasound-Triggered Mn-BaTiO₃ Nanoplatform for MRI-Guided Piezocatalytic Therapy

Recent studies highlight piezocatalytic therapy (PCT) as a superior curative strategy owing to its stable dynamic control compared to sonoluminescence-activated sonodynamic therapy (SDT). However, most nano-piezoelectric catalysts' catalytic efficiency in biosafety and biocompatibility is unsatisfactory. Herein, this study modifies the typical piezoelectric material tetragonal barium titanate (T-BTO). It introduces novel manganese (Mn) -coated T-BTO nanoparticles (MCTB) that possess magnetic resonance imaging (MRI) ability and enhanced PCT effects. The encapsulation of Mn masks the piezoelectric effect of the nanoparticles, and the acidic tumor microenvironment (TME) triggers the stripping of Mn and restoration of the piezoelectric effect of T-BTO, which produces ROS under ultrasonic irradiation. The presence of Mn ions also enhances the MRI property of the tumor site as a contrast agent. Additionally, ultrasonic irradiation promotes the conversion of low-valence Mn into a high-valence state, further stimulating ROS production. The biosafety, therapeutic effects, T1-weighted MRI, and piezoresponse of MCTB are investigated in vitro. Animal studies also indicate that the nanoparticles display good treatment performance when activated by ultrasound and guided by MRI. Therefore, this study develops an MCTB particle that boosts ROS generation, enables tumor-specific ROS release, and enhances T1-weighted MRI, offering a safe PCT approach for tumors.