Protease-Activatable Nanozyme with Photoacoustic and Tumor-Enhanced Magnetic Resonance Imaging for Photothermal Ferroptosis Cancer Therapy |
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Authors: | Wen Qin Jinzhao Huang Chunsheng Yang Quer Yue Shizhen Chen Mengdie Wang Shangbang Gao Xin Zhou Xiangliang Yang Yan Zhang |
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Affiliation: | 1. National Research Centre for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074 P. R. China;2. State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics Innovation Academy of Precision Measurement Science and Technology, Chinese Academy of Sciences, Wuhan, 430071 P. R. China;3. Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue, Wuhan, 430022 P. R. China;4. National Research Centre for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074 P. R. China
Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medical, Huazhong University of Science and Technology, Wuhan, 430074 P. R. China |
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Abstract: | Despite the promise of ferrotherapy in cancer treatment, current ferrous therapeutics suffer from compromised antitumor ferroptosis efficacy and low specificity for tumors. Herein, a protease-activatable nanozyme (Fe3O4@Cu1.77Se) is reported for photoacoustic and tumor-enhanced magnetic resonance imaging (MRI)-guided second near-IR photothermal ferroptosis cancer therapy. Fe3O4@Cu1.77Se remains stable in physiological conditions, but disintegrates to increase reactive intratumoral ferrous supply for elevated hydroxyl radical generation by Fenton reaction and GSH depletion in response to overexpressed matrix metalloproteinases in tumor microenvironment, leading to amplified ferroptosis of tumor cells as well as enhanced T2-weighted MRI contrast. Further integration with second near-IR photoirradiation to generate localized heat not only triggers effective photothermal therapy and photoacoustic imaging but more importantly, potentiates Fenton reaction to promote ferroptotic tumor cell death. Such synergism leads to the polarization of tumor-associated macrophage from the tumor-promoting M2 type to the tumor-killing M1 type, and induces the immunogenic cells death of tumor cells, which in turn promotes the maturation of dendritic cells and infiltration of cytotoxic T lymphocytes in tumor, contributing to significant tumor suppression. This study presents a novel activatable ferrous nanotheranostics for spatial-temporal control over antitumor ferroptosis responses. |
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Keywords: | photoacoustic imaging photothermal ferroptosis cancer therapy protease-activatable nanozymes tumor-enhanced magnetic resonance imaging |
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