An Ultrasmall SnFe2O4 Nanozyme with Endogenous Oxygen Generation and Glutathione Depletion for Synergistic Cancer Therapy

Abstract The tumor microenvironment (TME) with the characteristics of severe hypoxia, overexpressed glutathione (GSH), and high levels of hydrogen peroxide (H 2 O 2 ) dramatically limits the antitumor efficiency by monotherapy. Herein, a novel TME‐modulated nanozyme employing tin ferrite (SnFe 2 O 4 , abbreviated as SFO) is presented for simultaneous photothermal therapy (PTT), photodynamic therapy (PDT), and chemodynamic therapy (CDT). The as‐fabricated SFO nanozyme demonstrates both catalase‐like and GSH peroxidase‐like activities. In the TME, the activation of H 2 O 2 leads to the generation of hydroxyl radicals (•OH) in situ for CDT and the consumption of GSH to relieve antioxidant capability of the tumors. Meanwhile, the nanozyme can catalyze H 2 O 2 to generate oxygen to meliorate the tumor hypoxia, which is beneficial to achieve better PDT. Furthermore, the SFO nanozyme irradiated with 808 nm laser displays a prominent phototherapeutic effect on account of the enhanced photothermal conversion efficiency (η = 42.3%) and highly toxic free radical production performance. This “all in one” nanozyme integrated with multiple treatment modalities, computed tomography, and magnetic resonance imaging properties, and persistent modulation of TME exhibits excellent tumor theranostic performance. This strategy may provide a new dimension for the design of other TME‐based anticancer strategies.