Nanopiezoelectric Catalysis Enhancing Antibacterial Behavior Of Macrophages Against S. Aureus

Bacterial infections, particularly those caused by S. aureus, lead to high mortality, exacerbated by antibiotic resistance and immune evasion. This study aimed to enhance macrophage-mediated antimicrobial activity by simulating mitochondrial ROS (mROS) production using piezo-nanoparticles (BTAu@MPN). Synthesis of BTAu@MPN and investigation of its piezoelectric catalytic activity. Lysosomal escape ability of BTAu@MPN in BMDMs was studied via CLSM and electron microscopy, while its intracellular piezoelectric catalysis was assessed via flow cytometry, ROS staining. Phagocytic and intracellular antibacterial abilities of piezo-engineered macrophages were evaluated using flow cytometry, CLSM, with RNA sequencing to explore the underlying mechanisms. Mouse subcutaneous abscess model (Ethics No. 20220352) was established, and the antibacterial potential was assessed through immunofluorescence, abscess imaging, inflammatory factor detection, and tissue staining. Piezoelectric catalysis of BTAu was controlled by the acid-responsive properties of MPN coating. BTAu@MPN achieved lysosomal escape, improved the level of mROS driven by ultrasound. Piezo-engineered macrophages could activate the innate immune-proinflammatory response, phagocytic and intracellular bactericidal abilities of S. aureus were enhanced. BTAu@MPN had obvious ability to clear bacterial infection in the subcutaneous abscess model of S. aureus infected mice In this work, we demonstrated an immunotherapy that utilizing MPN to achieve intracellular delivery of piezoelectric nanoparticles for collecting ultrasound energy within immune cells to simulate mROS production and enhance fight against S. aureus infection. It provided a new way to treat bacterial infectious diseases in a biocompatible, on-demand and non-invasive way.