Immunomodulation‐Enhanced Nanozyme‐Based Tumor Catalytic Therapy

Abstract

Nanozyme‐based tumor catalytic therapy has attracted widespread attention in recent years. However, its therapeutic outcomes are diminished by many factors in the tumor microenvironment (TME), such as insufficient endogenous hydrogen peroxide (H2O2) concentration, hypoxia, and immunosuppressive microenvironment. Herein, an immunomodulation‐enhanced nanozyme‐based tumor catalytic therapy strategy is first proposed to achieve the synergism between nanozymes and TME regulation. TGF‐β inhibitor (TI)‐loaded PEGylated iron manganese silicate nanoparticles (IMSN) (named as IMSN‐PEG‐TI) are constructed to trigger the therapeutic modality. The results show that IMSN nanozyme exhibits both intrinsic peroxidase‐like and catalase‐like activities under acidic TME, which can decompose H2O2 into hydroxyl radicals (•OH) and oxygen (O2), respectively. Besides, it is demonstrated that both IMSN and TI can regulate the tumor immune microenvironment, resulting in macrophage polarization from M2 to M1, and thus inducing the regeneration of H2O2, which can promote catalytic activities of IMSN nanozyme. The potent antitumor effect of IMSN‐PEG‐TI is proved by in vitro multicellular tumor spheroids (MCTS) and in vivo CT26‐tumor‐bearing mice models. It is believed that the immunomodulation‐enhanced nanozyme‐based tumor treatment strategy is a promising tool to kill cancer cells.

Stimuli‐Responsive Manganese Single‐Atom Nanozyme for Tumor Therapy via Integrated Cascade Reactions

“…Inspired by the natural choice, Mn‐based nanozymes have widely attracted the attention of researchers in recent years. Various Mn‐based nanozymes have demonstrated different enzyme‐like activities, [14] such as glutathione peroxidase (GPx), [15] catalase (CAT), [14b, 16] superoxde dismutase (SOD) [17] and peroxidase (POD) [16a, 18] . Mn‐based nanozymes with multi‐enzyme activity have been used for the modulation of nitric oxide levels in mammalian cells [14d] .…”

Chemodynamic nanomaterials for cancer theranostics

“…It is also well known that the TGF-β inhibitor can regulate the TME to induce macrophage polarization from M2 to M1, which can regenerate H 2 O 2 . Thus, the TGF-β inhibitor has been loaded into the PEGylated iron manganese silicate NPs (IMSN) to trigger the synergistic cancer therapy [ 216 ]. The IMSN exhibited both peroxidase-like and catalase-like activities in the acidic TME, thus generating •OH and O 2 , respectively.…”

Nanomaterials Enhance the Immunomodulatory Effect of Molecular Targeted Therapy

“…127 Several studies using nanomaterials to combine TGF-β inhibitors with other treatments have achieved satisfactory results. 128,129 Xu et al designed an immunomodulation-enhanced nanozyme-based tumor catalytic therapy strategy by loading a TGF-β inhibitor in PEGylated iron manganese silicate nanoparticles (IMSN-PEG-TI NPs) (Figure 7). 129 The DLC of this TGF-β inhibitor was 3.40%.…”

“…128,129 Xu et al designed an immunomodulation-enhanced nanozyme-based tumor catalytic therapy strategy by loading a TGF-β inhibitor in PEGylated iron manganese silicate nanoparticles (IMSN-PEG-TI NPs) (Figure 7). 129 The DLC of this TGF-β inhibitor was 3.40%. In the acidic TME, Fe and Mn ions were released from the IMSN-PEG-TI NPs and catalyzed H 2 O 2 decomposition to produce hydroxyl radicals (•OH) and oxygen.…”