Phosphatidylserine-modified extracellular vesicles encapsulating prednisolone for targeted drug delivery to pulmonary macrophages in acute lung injury

Acute lung injury (ALI) remains a significant challenge in clinical medicine, characterized by severe inflammation and progressive tissue damage that demand innovative therapeutic solutions. Extracellular vesicles (EVs), derived from macrophages, have emerged as promising drug delivery vehicles due to their biocompatibility and inherent targeting properties. Building on this foundation, our study explores the development of phosphatidylserine-modified EVs (PS-EVs) encapsulating prednisolone (Pre) to enhance pulmonary macrophage targeting and mitigate inflammation in ALI. The core focus of this research was to address the limitations of conventional ALI treatments, including insufficient drug accumulation in inflamed lung tissues and systemic side effects. Here, we show that PS-EVs@Pre exhibit superior targeting ability and sustained drug release, resulting in significantly improved therapeutic efficacy and reduced pulmonary inflammation in ALI mouse models. Our findings not only validate the hypothesis that PS modification enhances macrophage-specific targeting but also highlight how this approach updates current drug delivery paradigms by achieving localized therapy with minimal systemic toxicity. These results advance the field of targeted drug delivery systems and open new avenues for applying EV-based therapies in other inflammatory diseases.