Hydrogen Incorporation Selectively Modulates the Catalytic Performance of Pd Nanozymes for Cascade-Catalytic Tumor Therapy

Pd-based nanozymes have emerged as promising alternatives to natural enzymes, but their application is still constrained due to suboptimal activity and poor specificity. As efficient hydrogen storage nanomaterials, the specific implications of implanted hydrogen on the enzyme-mimicking activity of Pd-based nanomaterials remain largely uninvestigated. In this study, we discovered that hydrogenation process significantly enhances the enzyme-like activity of Pd-based nanomaterials, although reaction specificity varies in dependence on the synthetic route of Pd hydrides. Pd/H2 nanocubes (NCs), which are synthesized by directly injecting hydrogen gas into a solution containing Pd NCs, exhibit a selective enhancement in antioxidative activity against cytotoxic hydrogen peroxide (H2O2), superoxide anion (O2•-), and hydroxyl radical (•OH) due to the sustained release of bioreductive hydrogen. In contrast, stable Pd hydride NCs, which are prepared through the in situ catalytic decomposition of alternative sources of hydrogen atoms, exhibit a remarkable enhancement in exclusive H2O2 activation pathways, specifically exhibiting peroxidase (POD)-like and catalase (CAT)-like activities. Multiple spectroscopic characterizations and density functional theory (DFT) calculations confirmed that this high catalytic activity and specificity of PdH NCs arise from lattice tensile strain and electronic structure change. Based on these findings, a PdH/glucose oxidase (GOx) nanocomplex was developed for cascade catalysis in tumor therapy. This work not only reveals that hydride formation can influence both the activity and selectivity of Pd nanozymes but also provides a viable strategy for the precise regulation of specific enzyme-like activity in hydrogen-loading nanozymes.