An Inhalable Apoptosis-Mimicking Functionalized Carbon Dots-Methylprednisolone Nanomedicine for Synergistic Therapy in Acute Lung Injury.

Acute lung injury (ALI) is a life-threatening inflammatory syndrome closely associated with reactive oxygen species (ROS) burst and dysregulation of M1/M2 macrophage polarization. Therefore, immune regulation of pulmonary macrophages represents a potential strategy to alleviate lung damage. However, existing approaches suffer from imprecise cellular targeting, monofunctional therapeutic effects, and suboptimal biocompatibility. To address these issues, an inhalable, multifunctional biomimetic nanoplatform is proposed that mimics apoptotic bodies (CTM@PS-Lip). CTM@PS-Lip is synthesized by fabricating nanoscale liposomes based on the outer leaflet structure of apoptotic cell membranes and encapsulating ROS responsive carbon dots (CDs)-methylprednisolone (MP) conjugates. Upon inhalation, liposomes rich in phosphatidylserine (PS) can transmit the "eat me" signal, efficiently inducing macrophages to recognize and phagocytose. Subsequently, the high ROS microenvironment in ALI-affected lung tissues triggers the controlled cargo release for: not only promoting the MP-mediated immunomodulatory effects by inhibiting M1 macrophage polarization and inducing M2 macrophage polarization but also synergizing with the potent CDs mediated ROS-scavenging capacity, significantly reducing pulmonary inflammation and promoting tissue repair. Thus, CTM@PS-Lip integrates imaging, therapy, and biosafety, proving to be a promising strategy for safe and efficient management in ALI.