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 (•O₂⁻) 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.