Fruit derived superoxide dismutase nanozyme for sepsis-induced acute lung injury therapy

As a life-threatening infectious disease in clinics, sepsis is characterized by uncontrolled systemic inflammatory response and multi-organ damage due to the excessive production of reactive oxygen species (ROS). The lung is the most frequently affected organ that is susceptible to developing acute lung injury (ALI) with high morbidity and mortality rates. Nevertheless, there are currently no effective drugs for the treatment of ALI. Herein, we developed a natural superoxide dismutase-mimicking carbon dots (H-CDs) derived from a fruit, hawthorn, with distinctive ROS scavenging ability for ALI therapy. The carboxyl/oxygen-based groups give the generated H-CDs excellent SOD-like activity of > 9000 U mg-1 and acted as a SOD-like nanozyme in the protection of cells from oxidative damage by scavenging ROS and ameliorating the levels of pro-inflammatory factors. Importantly, H-CDs reduced lung inflammatory response, oxidative damage, and histological severity in a lipopolysaccharide (LPS)-induced ALI mice model with minimal adverse effects. Mechanistically, H-CDs protected lung tissues by activating Nrf-2/HO-1 mediated antioxidant signaling and inhibiting NF-?B-dependent inflammatory responses. Collectively, this study establishes the potential of H-CDs as a promising therapeutic agent for the treatment of ALI. Overall design: RAW264.7 cells were cultured in a 6 wells plate in LPS (1 ug/ml) containing medium for 6 h supplemented with or without H-CDs (400 ug/ml), and total RNA was extracted using the TRIzol reagent. RNA sequencing was conducted using the Bioanalyzer 2100 system (Agilent Technologies, CA, USA).