Interfacial regulation of glutathione redox reaction by nanobubbles

Redox homeostasis is essential for the proper functioning of biological systems, and its disruption by excessive reactive oxygen species (ROS) underlies the pathogenesis of numerous diseases. Gas–liquid interfaces, owing to their unique physicochemical characteristics, can enrich ROS and thereby modulate oxidative reactions. Nanobubbles (NBs), with nanoscale gas domains suspended in aqueous solutions, present a high surface-to-volume ratio, offering abundant interfacial area with potential for ROS regulation. Though lots of evidences suggest that the NBs do play important antioxidative or prooxidative effects, the mechanisms by which NBs influence redox chemistry remain elusive. Herein, we evaluated the oxidative response of the model molecule glutathione (GSH) and a GSH-derived amphiphilic copolymer (ECGFF) to ROS in the presence of NBs of varying sizes. Our study reveals a striking size and substrate-specific redox modulation: normal-sized NBs (∼100–400 nm) suppressed oxidation of hydrophilic GSH but promoted oxidation of hydrophobic ECGFF; In contrast, ultra-small NBs (<50 nm) exerted antioxidative effects on both substrates. These results suggest that the interplay between NBs size, interfacial radical accumulation, and substrate hydrophobicity governs redox behavior at the gas-liquid interface. The insight of this mechanism not only advances our understanding of NBs-mediated redox processes but also offers a foundation for the rational design of NBs-based antioxidant strategies across diverse fields, including biomedicine, materials science, chemical engineering, and food technology.