Nitrogen-phosphorous co-doped carbonized chitosan nanoparticles for chemotherapy and ROS-mediated immunotherapy of intracellular Staphylococcus aureus infection

Staphylococcus aureus (S. aureus) residing in host macrophages is hard to clear because intracellular S. aureus has evolved mechanisms to hijack and subvert the immune response to favor intracellular infection. To overcome this challenge, nitrogen-phosphorous co-doped carbonized chitosan nanoparticles (NPCNs), which possess the polymer/carbon hybrid structures, were fabricated to clear intracellular S. aureus infection through chemotherapy and immunotherapy. Multi-heteroatom NPCNs were fabricated through the hydrothermal method, where chitosan and imidazole were used as the C and N sources and phosphoric acid as the P source. NPCNs can not only be used as a fluorescent probe for bacteria imaging but also kill extracellular and intracellular bacteria with low cytotoxicity. NPCNs could generate ROS and polarize macrophages into classically activated (M1) phenotypes to increase antibacterial immunity. Furthermore, NPCNs could accelerate intracellular S. aureus-infected wound healing in vivo. We envision that these carbonized chitosan nanoparticles may provide a new platform for clearing intracellular bacterial infection through chemotherapy and ROS-mediated immunotherapy.