GSH‐Depleted Nanozymes with Dual‐Radicals Enzyme Activities for Tumor Synergic Therapy

Abstract Although inspiring progress has been achieved in tumor nanocatalytic therapies based on tailor‐made nanozymes for converting hydrogen peroxide into reactive oxygen species (ROS) efficiently, most cytotoxic hydroxyl radicals do not spread far enough within a cell to damage the primary organelles for effective tumor therapy due to their short half‐life time (≈1 µs). Developing a novel nanocatalyst platform involving longer half‐life time ROS is desired. To this end, Fe 3 O 4 ‐Schwertmannite nanocomposites (Fe 3 O 4 ‐Sch) with triple‐effect tumor therapy are constructed through a facile method. The Schwertmannite shell converts the • OH produced by Fe 3 O 4 via the Fenton reaction into sulfate radicals with a longer half‐life time (30 µs). Combination of dual radicals exhibits overwhelming tumor inhibition efficacy. The nanocomposites also show the multifunctionality of good photothermal efficiency (33.2%) and synergistic oxidative stress amplification upon glutathione biosynthesis (GSH) depletion by the l ‐buthionine sulfoximine (BSO) molecules loaded in the hollow Fe 3 O 4 cores. The comprehensive properties of the nanoplatform including the dual‐radical production, Fe 3 O 4 nanocrystal mediated PTT, and the BSO mediated GSH depletion result in remarkable tumor inhibition both in vitro and in vivo, which may pave a way to constructing a synergic catalytic nanoplatform for efficient tumor therapy.