Sulfhydryl Sulfobetaine Stabilized Palladium Nanoparticles with High Peroxidase-like Activity for Enhanced Glutathione Detection and Tumor Suppression

Glutathione (GSH)-responsive nanozymes have attracted increasing attention for biosensing and cancer therapy. However, their practical applications are often limited by aggregation and insufficient catalytic activity. Herein, we report a zwitterionic sulfobetaine-modified palladium nanozyme (SH-SB/Pd NPs) that addresses these limitations by integrating high catalytic activity. The zwitterionic ligand simultaneously stabilizes Pd nanoparticles and preserves accessible catalytic sites, resulting in markedly enhanced peroxidase-like activity. SH-SB/Pd NPs efficiently catalyze H2O2 decomposition to generate multiple reactive oxygen species (1O2, O2•− and •OH), enabling favorable affinity for TMB (Km(TMB) = 0.28) and sensitive colorimetric GSH detection with a low detection limit of 0.135 μM. Benefiting from their long-term antifouling properties and ROS-generating capability, SH-SB/Pd NPs also exhibit potent antitumor activity, achieving 76.56% inhibition of HeLa cells under 808 nm laser irradiation. This work establishes a zwitterionic nanozyme platform that improves catalytic activity, stability, and therapeutic performance, offering a promising strategy for biosensing and synergistic cancer therapy.