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Endogenous/exogenous dual-responsive nanozyme for photothermally enhanced ferroptosis-immune reciprocal synergistic tumor therapy

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机构: [1]Department of Oncology & Cancer Institute, Sichuan Provincial People’s Hospital, and School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, P. R. China. [2]TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shi-er-qiao Road, Chengdu 610072, Sichuan, P. R. China. [3]Department of Urology, Deyang People’s Hospital, Deyang 618099, Sichuan, P. R. China
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Apoptosis resistance and immune evasion of tumor cells substantially increase the risk of cancer treatment failure. Here, a multifunctional nanozyme MET-CMS@FeTA (MCMSFT) formulated to induce nonapoptotic ferroptosis and boost immune recognition/attack, where compensatory mechanisms collectively overcome intrinsic tumor therapeutic limitations and improve medical intervention outcomes. Leveraging the multienzyme-like activity of MCMSFT to achieve oxygen generation, hydroxyl radical production, and glutathione depletion promotes hypoxia relief and triggers apoptosis/ferroptosis. Notably, MCMSFT-mediated photothermal therapy (PTT) facilitates direct tumor thermal ablation and offers exogenous heat to accelerate nanocatalytic reactions. Furthermore, PTT/ferroptosis-caused immunogenic cell death favors antitumor immunity initiation. Simultaneously, metformin administration and hypoxia amelioration down-regulate programmed death ligand 1 alleviating immune evasion. Interferon-gamma secretion poses positive feedback to ferroptosis, thereby establishing a ferroptosis-immune mutual amplification loop. Antitumor performances illustrate that MCMSFT eliminates primary tumors and suppresses metastasis/rechallenge tumors. Collectively, MCMSFT surmounts the predicament of apoptosis resistance and immune evasion in cancer treatment to acquire more effective and comprehensive therapy efficacy.

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基金编号: 52372263 12132004 32471367 32171395 2022NSFSC0048 UESTCY03023206100226

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大类 | 1 区 综合性期刊
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Q1 MULTIDISCIPLINARY SCIENCES
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Q1 MULTIDISCIPLINARY SCIENCES

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第一作者机构: [1]Department of Oncology & Cancer Institute, Sichuan Provincial People’s Hospital, and School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, P. R. China.
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通讯机构: [1]Department of Oncology & Cancer Institute, Sichuan Provincial People’s Hospital, and School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, P. R. China. [2]TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shi-er-qiao Road, Chengdu 610072, Sichuan, P. R. China. [3]Department of Urology, Deyang People’s Hospital, Deyang 618099, Sichuan, P. R. China
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