An Ultrasound Activated Vesicle of Janus Au‐MnO Nanoparticles for Promoted Tumor Penetration and Sono‐Chemodynamic Therapy of Orthotopic Liver Cancer

Sonodynamic therapy (SDT) has the advantages of high penetration, non-invasiveness, and controllability, and it is suitable for deep-seated tumors. However, there is still a lack of effective sonosensitizers with high sensitivity, safety, and penetration. Now, ultrasound (US) and glutathione (GSH) dual responsive vesicles of Janus Au-MnO nanoparticles (JNPs) were coated with PEG and a ROS-sensitive polymer. Upon US irradiation, the vesicles were disassembled into small Janus Au-MnO nanoparticles (NPs) with promoted penetration ability. Subsequently, GSH-triggered MnO degradation simultaneously released smaller Au NPs as numerous cavitation nucleation sites and Mn²⁺ for chemodynamic therapy (CDT), resulting in enhanced reactive oxygen species (ROS) generation. This also allowed dual-modality photoacoustic imaging in the second near-infrared (NIR) window and T₁ -MR imaging due to the released Mn²⁺ , and inhibited orthotopic liver tumor growth via synergistic SDT/CDT.