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 (H2O2) dramatically limits the antitumor efficiency by monotherapy. Herein, a novel TME‐modulated nanozyme employing tin ferrite (SnFe2O4, 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 H2O2 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 H2O2 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.

Recent Advances in Nucleic Acid Modulation for Functional Nanozyme

“…(4) Nanozymes have high catalytic activity and excellent biocompatibility. Nanozymes have been used as antibacterial agents to promote wound healing [130,131]; to assist in tumor cell therapy (such as magnetic hyperthermia, chemodynamic therapy, photothermal therapy, and photodynamic therapy [132][133][134][135][136]); and to alleviate the symptoms of metabolic diseases (such as glucose metabolism: diabetes [45], immune metabolism: inflammation and cancer [137,138]). Most of the nanozymes reported are metal oxides (such as iron oxide, manganese oxide, copper oxide, cerium oxide, etc.)…”

γ-Glutamyl transpeptidase-activatable near-infrared nanoassembly for tumor fluorescence imaging-guided photothermal therapy

“…As synthesized nanoparticles were characterized by transmission electron microscope (TEM), dynamic light scattering (DLS), and Zeta potential analyzer. The hydrodynamic size of nanoparticles was observed from a DLS study 34 .…”

A Ferrocene‐Functionalized Covalent Organic Framework for Enhancing Chemodynamic Therapy via Redox Dyshomeostasis

“…The most common method for enhancing CDT performance is chemical depletion of intracellular GSH. Sulphydryl‐reactive agents, such as Cu(II), [ 8 ] SnFe 2 O 4 , [ 9 ] Bi 2 S 3 , [ 10 ] NiS 2 , [ 11 ] maleimide, [ 12 ] and p ‐quinone methide, [ 13 ] can react with biological thiols (e.g., GSH and cysteine) to weaken the cell antioxidant capacity and improve the effect of CDT. However, as the most abundant antioxidant found in living organisms, GSH in tumor cells is maintained at a high levels (about 5 × 10 −3 m ), [ 14 ] which places a high demand on the cellular uptake of exogenous agents.…”