Inflammation-targeting and self-limited neutrophilic membrane-encapsulated teicoplanin for the treatment of infectious pneumonia.

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) pneumonia has a high clinical incidence and is associated with a significant mortality risk. The existence of intracellular pathogens and the infection-induced swarming of neutrophils exacerbate the challenges in treating pneumonia. Here, we addressed these issues by developing a platform based on neutrophilic membrane-camouflaged teicoplanin (Teic@NEV) to kill bacteria in tissue and prevent inflammatory lung injury associated with MRSA pneumonia. Teic@NEV improved the efficiency of drug entry into cells, meaningfully increasing the intracellular drug concentration in infected cells and eliminating intracellular MRSA. Moreover, Teic@NEV enhanced the penetration of teicoplanin into the biofilm and improved antimicrobial and antibiofilm activities in vitro. Surprisingly, Teic@NEV delivered teicoplanin specifically to sites of inflammation and reduced lung injury by hindering neutrophil swarming in vivo. Thus, this platform represents an effective strategy to limit neutrophil swarming and kill intracellular pathogens in patients with MRSA pneumonia, demonstrating its significant potential for use in clinical practice.