ROS-responsive nanoparticles for bioimaging and treating acute lung injury by releasing dexamethasone and improving alveolar macrophage homeostasis

Acute lung injury (ALI) triggers the activation of pulmonary macrophages, which in turn produce excessive amounts of reactive oxygen species (ROS). We synthesized ROS-responsive red light-emitting carbon dots (RCMNs) that target lung macrophages, possess bioimaging capabilities, and efficiently eliminate intracellular ROS, thereby demonstrating anti-inflammatory effects for treating acute lung injury (ALI). In an LPS-induced ALI mouse model, RCMNs showed bioimaging and therapeutic potential, reducing lung damage and inflammation by targeting ROS-damaged tissue. RCMNs also improved alveolar macrophage activity, decreased inflammatory cytokines (TNF-α and IL-6), and enhanced survival in endotoxic shock, indicating their therapeutic potential for ALI. RNA-seq analysis revealed that RCMNs modulate signaling pathways related to calcium, TNF, and Toll-like receptors, highlighting their role in regulating inflammation and immune responses. Mechanistically, RCMNs alleviate inflammation in ALI by enhancing mitochondrial function in lung macrophages, as evidenced by improved mitochondrial morphology and membrane potential. This protective effect is mediated through the regulation of intracellular Ca2+ levels and mitochondrial respiratory chain complexes, suggesting RCMNs as a therapeutic strategy for mitochondrial dysfunction in ALI.