Honeysuckle‐Derived Carbon Dots With Robust Catalytic and Pharmacological Activities for Mitigating Lung Inflammation by Inhibition of Caspase11/GSDMD‐Dependent Pyroptosis

Abstract The catalytic activity of carbon dots (CDs) has generated significant interest regarding their potential applications within the biomedical field. However, the structure‐activity relationship of CDs and their pharmacological mechanisms in disease treatment have yet to be comprehensively elucidated. In this study, two distinct types of CDs exhibiting superoxide dismutase (SOD)‐like enzymatic activities are synthesized through hydrothermal (Hy‐CDs) and carbonization (Ca‐CDs) methods, utilizing Honeysuckle as the common carbon material precursor. Through comparative analysis, surface group modifications, and theoretical calculations, it is determined that the SOD‐like enzymatic activity of CDs primarily originated from the stabilizing influence of the amino group on the superoxide (•O 2 − ) intermediate and its conjugation to the π‐system, facilitating electron transfer. In vitro experiments demonstrated that Hy‐CDs effectively alleviated cellular oxidative stress and inhibited the secretion of pro‐inflammatory cytokines. Furthermore, the significant bioactivity and catalytic properties of Hy‐CDs contribute to their pronounced therapeutic efficacy in the treatment of acute lung injury (ALI) and lung ischemia/reperfusion injury (LIRI). Guided by transcriptomic analysis and Western blotting, it is demonstrated that Hy‐CDs effectively inhibit Caspase11/GSDMD‐dependent non‐classical pyroptosis by down‐regulating GBP2 protein expression, thereby contributing to lung inflammation. This study elucidates the structure‐activity relationship and underlying biological mechanisms of Hy‐CDs in therapeutic applications.