Abstract
Although extensive antibiotic regimens have been implemented to address pathogen-infected pneumonia, existing strategies are constrained in their efficacy against intracellular bacteria, a prominent contributor to antibiotic resistance. In addition, the concurrent occurrence of a cytokine storm during antibiotic therapy presents a formidable obstacle in the management of pneumonia caused by pathogens. In the present study, an infection-targeting system that leverages M2-macrophage-derived vesicles [exosomes (Exos)] as vehicles to convey antibiotics (antibiotics@Exos) was developed for effective pneumonia management. The proposed system can enable antibiotics to be specifically delivered to infected macrophages in pneumonia through homotypic recognition and was found to exhibit an exceptional intracellular bactericidal effect. Moreover, M2-type vesicles exhibit a high degree of efficiency in reprogramming inflammatory macrophages toward an anti-inflammatory phenotype. As a result, the administration of antibiotics@Exos was found to substantical decrease the level of the infiltrated inflammatory cells and alleviate the inflammatory factor storm in the lungs of acute lung injury mice. This intervention resulted in the alleviation of reactive-oxygen-species-induced damage, reduction of pulmonary edema, and successful pneumonia treatment. This bioactive vesicle delivery system effectively compensates for the limitations of traditional antibiotic therapy regimens with pluralism effects, paving a new strategy for serious infectious diseases, especially acute pneumonia treatment.