Immunomodulation-Enhanced Nanozyme-Based Tumor Catalytic Therapy |
| |
| Authors: | Bolong Xu Yan Cui Weiwei Wang Shanshan Li Chengliang Lyu Shuang Wang Weier Bao Hongyu Wang Meng Qin Zhen Liu Wei Wei Huiyu Liu |
| |
| Affiliation: | 1. Beijing Advanced Innovation Center for Soft Matter Science and Engineering, State Key Laboratory of Organic-Inorganic Composites, Bionanomaterials & Translational Engineering Laboratory, Beijing Key Laboratory of Bioprocess, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing, 100029 China;2. Beijing Advanced Innovation Center for Soft Matter Science and Engineering, State Key Laboratory of Organic-Inorganic Composites, Bionanomaterials & Translational Engineering Laboratory, Beijing Key Laboratory of Bioprocess, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing, 100029 China State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190 China;3. State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190 China |
| |
| 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. |
| |
| Keywords: | catalase-like activity immunomodulation nanozymes peroxidase-like activity tumor catalytic therapy |
|
|
