Turning Silica into Enzymes by Hydrogenation: Simultaneously Achieving Oxygen Vacancy Engineering and Tumor Adaptive Accumulation for NIR‐II‐Potentiated Therapy

Abstract Molybdenum (Mo)‐based nanozymes have been attracting increasingly extensive attention in photocatalytic antitumor field due to their versatile physicochemical properties, whereas the limited light capture rate and high recombination rate of photogenerated carriers seriously impedes their further development. Herein, MoO 3 ‐starring silica nanozymes with hyaluronic acid modification (HMMSNs@HA) are innovated by hydrogenation to simultaneously achieve oxygen vacancies (OVs) engineering and tumor adaptive accumulation for the second near‐infrared (NIR‐II, 1064 nm) light‐potentiated thermal‐catalytic therapy. The hydrogenation‐regulated OVs can narrow the band gap of HMMSNs from 2.66 to 1.16 eV, achieving optimal optical absorption in NIR‐II region. Additionally, HMMSNs hold high separation efficacy of electron‐hole pairs to facilitate the generation of reactive oxygen species under laser irradiation. Significantly, HMMSNs@HA are stable in tumor microenvironment, while can degrade in normal physiological conditions, thereby offering tumor‐adaptive accumulation. Synchrotron radiation‐based extended X‐ray absorption fine structure spectroscopy reveals that OVs enabling the Mo 4+ and Mo 5+ formation, which can react with tumor endogenous H 2 O 2 to produce hydroxyl radicals. Furthermore, OVs‐induced localized surface plasmon resonance effect endows the nanozymes with photothermal conversion efficacy of 32.3%, which affords NIR‐II‐excited photonic hyperthermia‐enhances catalytic therapy. All the experimental results demonstrate the high safety and superiorities of HMMSNs@HA for NIR‐II‐initiate therapy.