Intracellular delivery of piezotronic-dominated nanocatalysis to mimic mitochondrial ROS generation for powering macrophage immunotherapy

Macrophages are the first line of host defense against bacterial infections and mitochondrial reactive oxygen species (mROS) plays an important role in the bactericidal innate response of macrophages. In this work, we propose the concept of engineering macrophages with artificial mROS generation ability to combat bacterial infection, which is enabled by metal phenolic network-mediated lysosomal escape of piezocatalytic nanoparticles (piezoNPs) and piezotronic effect-enhanced intracellular piezocatalysis. By harvesting ultrasound energy, the engineered macrophages can demonstrate pro-inflammatory phenotype, potent phagocytosis and strong bactericidal activity against Staphylococcus aureus (S. aureus). By in situ engineering macrophages at the infection site with targeting ligand-modified piezoNPs, the treatment of S. aureus abscess is further demonstrated. This study reveals the potential of intracellular piezotronic nanocatalysis in enhancing innate immune response of macrophages, providing a non-invasive modulation of macrophages-mediated immunotherapy.