A pH-responsive mesoporous mPt/Fe²⁺ nanozyme with pH-switchable catalase-like activity for modulating H₂O₂/O₂...

Selective regulation and reliable monitoring of intracellular H₂O₂/O₂ homeostasis are important for understanding cellular redox processes, yet multifunctional nanozymes often exhibit competing enzyme-like activities that complicate their catalytic behavior under biologically relevant conditions. Herein, we developed a pH-responsive mesoporous platinum/ferrous ion (mPt/Fe²⁺) nanozyme with switchable oxidase-like (OXD-like), peroxidase-like (POD-like), and catalase-like (CAT-like) activities. Systematic catalytic characterization revealed distinct pH-dependent activity profiles, with the maximum OXD-like, POD-like, and CAT-like activities occurring at pH 3.0, 4.5, and 6.5, respectively. Notably, at pH 6.5, the OXD- and POD-like activities were strongly suppressed, whereas CAT-like activity predominated, enabling efficient decomposition of H₂O₂ into O₂ with reduced interference from competing catalytic pathways. Compared with pristine mPt, mPt/Fe²⁺ exhibited enhanced catalytic performance and a relatively high affinity toward H₂O₂. Kinetic analyses further demonstrated favorable substrate interactions and catalytic efficiency. Mechanistic studies using reactive oxygen species-responsive fluorescent probes revealed that ¹O₂ and •OH were involved in the POD-like pathway, whereas O₂ participated in the CAT-like pathway. Density functional theory calculations showed that Fe²⁺ incorporation strengthened H₂O₂ adsorption and decreased the key free-energy barriers for H₂O₂ decomposition, providing a molecular basis for the enhanced CAT-like activity. Furthermore, RDPP- and DCFH-DA-based fluorescence assays combined with confocal laser scanning microscopy demonstrated concentration-dependent intracellular O₂ generation and H₂O₂ depletion in tumor cells. This work establishes a pH-responsive nanozyme platform integrating catalytic switching, mechanistic analysis, and intracellular fluorescence imaging, offering a useful analytical strategy for probing and regulating cellular H₂O₂/O₂ homeostasis.