Niobium carbide MXenzyme for targeting disaggregation of human insulin fibrils and anti-inflammation

Human insulin (HI) fibrillation is a critical event in type II diabetes (T2D), and studying its disaggregation mechanism is an attractive strategy for treating this condition. Here we loaded quercetin onto niobium carbide (Nb 2 C), a type of MXene, to create Nb 2 C@QUE, which was shown in vitro to disaggregate HI fibrils rapidly. Nb 2 C@QUE binds and disaggregates HI fibrils in two stages within a short time frame, converting the highly ordered β-sheet structures into α-helix and random coil. Isothermal titration calorimetry (ITC) was used to determine the thermodynamic parameters of the entire system, revealing that the binding of Nb 2 C@QUE to HI fibrils occurs in two stages. Corresponding rapid fluorescence kinetics results demonstrated that Nb 2 C@QUE binds with HI monomers or fibrils at a second-level rate, with no intermediates formed during this process. Due to its excellent ability to eliminate reactive oxygen and nitrogen species (RONS), Nb 2 C@QUE also has the potential to act as a nanozyme (MXenzyme) to mitigate inflammation caused by HI fibrils, overcoming the limitations of traditional single-protein disaggregation agents. These findings provide insights into the mechanism of protein fibril disaggregation from a physicochemical perspective and offer guidance for designing multifunctional materials for protein fibril disaggregation and decomposition.