Inflammatory Endothelium‐Targeted Carbon Dot Nanozymes for Exogenous Enzyme Supplementation and Synergistic Regulation in Acute Lung Injury

ABSTRACT Acute lung injury (ALI) features vascular endothelial damage, impaired barrier function, and excessive ROS accumulation, which depletes endogenous peroxidases and disrupts redox homeostasis. Transcriptomic comparison between control and ALI model groups verified marked dysregulation of genes linked to oxidative stress, inflammation, and endothelial barrier dysfunction. To date, exogenous enzyme supplementation represents a necessary strategy for treating ALI, yet very few options are available to halt excessive ROS accumulation within the critical therapeutic time window. Here, we developed a nanozyme system (SCP@CD) capable of solving this problem by encapsulating autofluorescent Mn/S‐co‐doped carbon dots (CDs) into polymer micelles self‐assembled via a Schiff base formed by sialic acid‐modified chitosan oligosaccharide and protocatechualdehyde. As a targeting ligand, sialic acid enables active targeting of E‐selectin on inflamed endothelium, realizing enhanced fluorescence for noninvasive in vivo tracking. Chitosan oligosaccharide linked to sialic acid reduces systemic toxicity, while the Schiff base formed by chitosan oligosaccharide and protocatechualdehyde mediates pH‐responsive release via cleavage in acidic inflammatory microenvironments. SCP@CD functions as an exogenous enzyme supplementation via the multi‐nanozyme activities of CDs and achieves synergistic anti‐inflammatory and endothelial barrier‐repairing effects by regulating inflammatory mediators and junctional proteins. This platform offers a novel precision nanomedicine strategy for ALI.