Cysteine-Intercalated ZnFe-LDH as an Enhanced Peroxidase Nanozyme via Valence Regulation for Efficient Antibacterial Therapy

Developing peroxidase-like nanomaterials of high activity, low cost, and eco-friendliness remains a key challenge for effective and efficient antibacterial applications. Herein, of the reducibility and molecular simplicity, cysteine (Cys) was introduced into a zinc-iron-layered double hydroxide (ZnFe-LDH) to build the valence-regulated nanozyme (Cys-ZnFe-LDH). Via the reduction and intercalation, Cys-ZnFe-LDH was facile and mildly acquired with valence regulation and interlayer space enlargement, promoting the mass transfer rate and redox cycle, so as to enhance the catalytic performance. Significantly, intercalated with cysteine, the Fe²⁺/Fe³⁺ ratio increased from 1.42 to 3.27 in Cys-ZnFe-LDH, and also the specific surface areas enlarged from 48.989 to 79.445 m²/g. Notably, Cys-ZnFe-LDH remarkably enhanced H₂O₂ decomposition into hydroxyl radicals, with the maximum reaction velocity of 25.80 × 10⁻⁸ M·s⁻¹, as well as an extremely high affinity, favoring efficient •OH generation. However, leveraging such superior enzyme-mimicking activity, Cys-ZnFe-LDH possessed the potential broad-spectrum antibacterial performance, respectively, achieving 99% elimination of Escherichia coli (0.5 mM H₂O₂, 50 μg·mL⁻¹) and Staphylococcus aureus (0.1 mM H₂O₂, 100 μg·mL⁻¹), as well as a remarkable hemolysis rate and cell survival rate. Prospectively, Cys-ZnFe-LDH was a synergistic antibacterial "nanoknife" of the enhanced interfacial enrichment, Fe valence-state regulation, and •OH-driven oxidative damage.