Myeloperoxidase-mimetic nanozyme generates hypochlorous acid for phagosomal bacteria elimination

Fighting against intracellular bacteria that can evade antibiotics is a long-standing challenge. Inspired by the abundant production of hydrogen peroxide (H2O2) within phagosomes during phagocytosis of bacteria, we have devised a myeloperoxidase-like nanozyme capable of facilitating phagosomal reactive oxygen species (ROS) production within the phagosomal environment, while simultaneously enabling the intracellular delivery of antibiotics. These novel nanozymes, denoted as GEN-NPs, has been fabricated through the conjugation of gentamicin (GEN) onto ultrasmall vanadium oxide nanoparticles (NPs). Our results demonstrate that GEN-NPs exhibit superior efficiency in eradicating both intracellular and extracellular bacteria, surpassing free GEN or NPs alone. This enhanced bactericidal activity can be attributed to the bacteria targeting ability and synergistic effect of myeloperoxidase-like GEN-NPs, which catalyze the conversion of abundant H2O2 into bactericide hypochlorous acid (HClO) and ROS within phagosomes. Moreover, the superior therapeutic outcomes of GEN-NPs have been observed across multiple infection models, outperforming the combined effect of GEN and NPs. This study posits that myeloperoxidase-like nanozyme presents a versatile platform for the development of next-generation therapeutics targeting intracellular bacteria.