Cascade nanozyme of multi-antioxidant Mn-doped carbon dots counters cytokine storm in acute lung injury

Acute lung injury (ALI) remains a significant challenge due to its uncontrolled and complex inflammatory response. Current clinical drugs exhibit limited therapeutic efficacy, and prolonged use may lead to drug resistance, immune suppression, as well as systemic side effects. Therefore, there is an urgent necessity to develop innovative and safe therapies for mitigating inflammation in ALI. In this study, Mn-doped carbon dots (CDs) cascade nanozyme is constructed, VTMn-CDs, which targets VCAM-1 and exhibits multi-antioxidant enzyme activity for the precise treatment of ALI. Compared to previously reported CDs nanozymes, VTMn-CDs exhibit broad-spectrum antioxidant activity. Using the LPS-induced ALI mouse model, experimental results demonstrate the nanozyme's remarkable anti-inflammatory and antioxidant effects through pathological analysis and vascular permeability assays. VTMn-CDs effectively suppress alveolar inflammation and reduce tissue damage, with therapeutic effects comparable to dexamethasone. Mechanistic studies reveal that VTMn-CDs mitigated oxidative stress, downregulate inflammatory molecules by inhibiting the TLR/MyD88/NF-κB signaling pathway. VTMn-CDs provides a precise and targeted approach to the treatment of ALI by scavenging excess reactive oxygen species (ROS) and inhibiting the ability of inflammatory cell recruitment to the lung. The dual strategy of scavenging ROS and suppressing pro-inflammatory factor release, presents a promising therapeutic approach for improving ALI prognosis.