From Cold to Hot: Nanozyme-Based Strategies for Reprogramming the Tumour Immunoenvironment

Abstract

The immunosuppressive tumour immune microenvironment (TIME) is a fundamental barrier that renders “cold” tumours resistant to conventional cancer immunotherapies. Nanozymes, catalytic nanomaterials with enzyme-mimicking activities, have emerged as powerful and versatile agents for reprogramming the TIME and igniting robust antitumour immunity. This review systematically elucidates how nanozymes, through their multi-enzyme catalytic properties, orchestrate a multifaceted attack on the immunosuppressive TIME by regulating reactive oxygen species, alleviating hypoxia, depleting antioxidants, and inducing immunogenic cell death, ferroptosis, and cuproptosis. These catalytic actions collectively promote dendritic cell maturation, enhance cytotoxic T lymphocyte infiltration, and repolarise tumour-associated macrophages toward an M1 phenotype, thereby effectively converting immunologically “cold” tumours into “hot” ones. Furthermore, we deeply analyse the synergistic potential of nanozymes when integrated with established therapies—including immune checkpoint blockade, phototherapy, sonodynamic therapy, chemotherapy, and radiotherapy. Finally, by discussing advanced bioengineered platforms and addressing the ongoing challenges related to biosafety and clinical translation, we envision that nanozyme-based catalytic immunoengineering represents a paradigm-shifting approach for next-generation combinatorial cancer immunotherapy.

Keywords

cold tumours / combination therapies / immunogenic cell death / nanozymes / tumour immunoenvironments

References

[1] L. M. Liz-Marzán, A. E. Nel, C. J. Brinker, et al., “What Do we Mean When we Say Nanomedicine?,” ACS Nano 16, no. 9 (2022): 13257–13259.

[2] J. Wu, X. Wang, Q. Wang, et al., “Nanomaterials With Enzyme-Like Characteristics (Nanozymes): Next-Generation Artificial Enzymes (II),” Chemical Society Reviews 48, no. 4 (2019): 1004–1076.

[3] S. Jeyachandran, R. Srinivasan, T. Ramesh, A. Parivallal, J. Lee, and E. Sathiyamoorthi, “Recent Development and Application of “Nanozyme” Artificial Enzymes-A Review,” Biomimetics (Basel) 8, no. 5 (2023): 446.

[4] F. Manea, F. B. Houillon, L. Pasquato, and P. Scrimin, “Nanozymes: Gold-Nanoparticle-Based Transphosphorylation Catalysts,” Angewandte Chemie (International Ed. in English) 43, no. 45 (2004): 6165–6169.

[5] Y. Chen, Y. Cai, X. Yu, et al., “A Photo and tumour Microenvironment Activated Nano-Enzyme With Enhanced ROS Generation and Hypoxia Relief for Efficient Cancer Therapy,” Journal of Materials Chemistry B 9, no. 39 (2021): 8253–8262.

[6] P. Zhu, Y. Chen, and J. Shi, “Nanoenzyme-Augmented Cancer Sonodynamic Therapy by Catalytic tumour Oxygenation,” ACS Nano 12, no. 4 (2018): 3780–3795.

[7] H. Ge, J. Du, J. Zheng, et al., “Effective Treatment of Cisplatin-Resistant Ovarian tumours With a MoS2-Based Sonosensitizer and Nanoenzyme Capable of Reversing the Resistant-Microenvironment and Enhancing Ferroptosis and Apoptosis,” Chemical Engineering Journal 446 (2022): 137040.

[8] Z. Zhao, S. Dong, Y. Liu, et al., “tumour Microenvironment-Activable Manganese-Boosted Catalytic Immunotherapy Combined With PD-1 Checkpoint Blockade,” ACS Nano 16, no. 12 (2022): 20400–20418.

[9] M. Wu, K. Zhao, X. Tao, et al., “Biomimetic Copper Nanozyme Reprograms Cold tumour via Cuproptosis-Pyroptosis Crosstalk for Potent Renal Carcinoma Immunotherapy,” ACS Applied Materials & Interfaces 17, no. 20 (2025): 29291–29304.

[10] B. Yang, L. Cao, K. Ge, et al., “FeSA-Ir/Metallene Nanozymes Induce Sequential Ferroptosis-Pyroptosis for Multi-Immunogenic Responses Against Lung Metastasis,” Small 20, no. 42 (2024): e2401110.

[11] L. Sun, W. Gao, J. Liu, et al., “O(2)-supplying Nanozymes Alleviate Hypoxia and Deplete Lactate to Eliminate tumours and Activate Antitumour Immunity,” ACS Applied Materials & Interfaces 14, no. 51 (2022): 56644–56657.

[12] H. Liu, S. Jiang, M. Li, et al., “Dual Enzyme-Driven Cascade Reactions Modulate Immunosuppressive tumour Microenvironment for Catalytic Therapy and Immune Activation,” ACS Nano 18, no. 44 (2024): 30345–30359.

[13] Y. Zhao, G. Zhang, F. Yu, et al., “Cascading Catalytic Nanozyme Enhance Ferroptosis-Mediated Chemoimmunotherapy via the cGAS-STING and IL-6/STAT3 Pathways,” Chemical Engineering Journal 509 (2025): 161354.

[14] D. S. Chen and I. Mellman, “Elements of Cancer Immunity and the Cancer-Immune Set Point,” Nature 541, no. 7637 (2017): 321–330.

[15] D. Gaebler, S. J. Hachey, and C. C. W. Hughes, “Microphysiological Systems as Models for Immunologically ‘cold’ tumours,” Frontiers in Cell and Developmental Biology 12 (2024): 1389012.

[16] A. E. van Diepen, S. Kucukcelebi, J. de Vos-Geelen, and N. G. Kooreman, “Immunotherapy for Solid Tumours: Current Clinical Landscape and Future Directions,” European Surgical Research 67, no. 1 (2026): 21–29.

[17] Y. T. Liu and Z. J. Sun, “Turning Cold tumours Into Hot tumours by Improving T-Cell Infiltration,” Theranostics 11, no. 11 (2021): 5365–5386.

[18] S. Spranger, R. Bao, and T. F. Gajewski, “Melanoma-Intrinsic Beta-Catenin Signalling Prevents Anti-Tumour Immunity,” Nature 523, no. 7559 (2015): 231–235.

[19] L. P. Andrews, S. C. Butler, J. Cui, et al., “LAG-3 and PD-1 Synergize on CD8(+) T Cells to Drive T Cell Exhaustion and Hinder Autocrine IFN-Gamma-Dependent Anti-tumour Immunity,” Cell 187, no. 16 (2024): 4355–4372 e4322.

[20] A. R. Cillo, C. Cardello, F. Shan, et al., “Blockade of LAG-3 and PD-1 Leads to Co-Expression of Cytotoxic and Exhaustion Gene Modules in CD8(+) T Cells to Promote Antitumour Immunity,” Cell 187, no. 16 (2024): 4373–4388 e4315.

[21] S. F. Ngiow, S. Manne, Y. J. Huang, et al., “LAG-3 Sustains TOX Expression and Regulates the CD94/NKG2-Qa-1b Axis to Govern Exhausted CD8 T Cell NK Receptor Expression and Cytotoxicity,” Cell 187, no. 16 (2024): 4336–4354 e4319.

[22] X. Huang, R. Gu, Z. Li, and F. Wang, “Igniting Cold tumours: Multi-Omics-Driven Strategies to Overcome Immune Evasion and Restore Immune Surveillance,” Oncology Research 33, no. 10 (2025): 2857–2902.

[23] D. S. Shin, J. M. Zaretsky, H. Escuin-Ordinas, et al., “Primary Resistance to PD-1 Blockade Mediated by JAK1/2 Mutations,” Cancer Discovery 7, no. 2 (2017): 188–201.

[24] K. E. de Visser and J. A. Joyce, “The Evolving tumour Microenvironment: From Cancer Initiation to Metastatic Outgrowth,” Cancer Cell 41, no. 3 (2023): 374–403.

[25] P. Guha, K. R. Heatherton, K. P. O'Connell, I. S. Alexander, and S. C. Katz, “Assessing the Future of Solid tumour Immunotherapy,” Biomedicine 10, no. 3 (2022): 655.

[26] W. Lv, M. Cao, J. Liu, Y. Hei, and J. Bai, “tumour Microenvironment-Responsive Nanozymes Achieve Photothermal-Enhanced Multiple Catalysis Against tumour Hypoxia,” Acta Biomaterialia 135 (2021): 617–627.

[27] R. Zhang, Y. Li, H. Fu, et al., “Nanomedicine Strategies for Cuproptosis: Metabolic Reprogramming and tumour Immunotherapy,” Acta Pharmaceutica Sinica B 15, no. 9 (2025): 4582–4613.

[28] Z. Yan, Y. Bai, S. Zhang, et al., “Quasi Fe MIL-53 Nanozyme Inducing Ferroptosis and Immunogenic Cell Death for Cancer Immunotherapy,” Nature Communications 16, no. 1 (2025): 2290.

[29] Q. Fu, C. Wei, and M. Wang, “Transition-Metal-Based Nanozymes: Synthesis, Mechanisms of Therapeutic Action, and Applications in Cancer Treatment,” ACS Nano 18, no. 19 (2024): 12049–12095.

[30] X. Xu, Y. Zhang, C. Meng, et al., “Nanozymes in Cancer Immunotherapy: Metabolic Disruption and Therapeutic Synergy,” Journal of Materials Chemistry B 12, no. 37 (2024): 9111–9143.

[31] Q. He and L. Zhang, “Nanozyme-Driven Remodeling of the Immune Microenvironment: From Catalytic Therapy to Precise Immune Regulation,” Nanoscale 17, no. 45 (2025): 25947–25963.

[32] A. O. C. Iroegbu, M. L. Teffo, and E. R. Sadiku, “Cancer Therapy With Engineered Nanozymes: From Molecular Design to Tumour-Responsive Catalysis,” Nanomedicine (London, England) 20, no. 14 (2025): 1799–1817.

[33] W. Zhang, M. Wang, P. Ma, and J. Lin, “Recent Progress of Advanced Nanozymes for Targeted Oncotherapy and Synergistic Immunotherapy,” Coordination Chemistry Reviews 536 (2025): 216674.

[34] R. Breslow, “Biomimetic Chemistry and Artificial Enzymes: Catalysis by Design,” Accounts of Chemical Research 28, no. 3 (1995): 146–153.

[35] H. Wei and E. Wang, “Nanomaterials With Enzyme-Like Characteristics (Nanozymes): Next-Generation Artificial Enzymes,” Chemical Society Reviews 42, no. 14 (2013): 6060–6093.

[36] N. T. M. Thao, H. D. K. Do, N. N. Nam, N. K. S. Tran, T. T. Dan, and K. T. L. Trinh, “Antioxidant Nanozymes: Mechanisms, Activity Manipulation, and Applications,” Micromachines (Basel) 14, no. 5 (2023): 1017.

[37] Z. Chen, J. J. Yin, Y. T. Zhou, et al., “Dual Enzyme-Like Activities of Iron Oxide Nanoparticles and Their Implication for Diminishing Cytotoxicity,” ACS Nano 6, no. 5 (2012): 4001–4012.

[38] Q. Liu, A. Zhang, R. Wang, Q. Zhang, and D. Cui, “A Review on Metal- and Metal Oxide-Based Nanozymes: Properties, Mechanisms, and Applications,” Nano-Micro Letters 13, no. 1 (2021): 154.

[39] M. Zandieh and J. Liu, “Nanozyme Catalytic Turnover and Self-Limited Reactions,” ACS Nano 15, no. 10 (2021): 15645–15655.

[40] W. Gao, J. He, L. Chen, et al., “Deciphering the Catalytic Mechanism of Superoxide Dismutase Activity of Carbon Dot Nanozyme,” Nature Communications 14, no. 1 (2023): 160.

[41] Z. Yu, Q. Li, J. Wang, et al., “Reactive Oxygen Species-Related Nanoparticle Toxicity in the Biomedical Field,” Nanoscale Research Letters 15, no. 1 (2020): 115.

[42] S. Liang, X. Tian, and C. Wang, “Nanozymes in the Treatment of Diseases Caused by Excessive Reactive Oxygen Specie,” Journal of Inflammation Research 15 (2022): 6307–6328.

[43] A. K. Patlolla, D. Hackett, and P. B. Tchounwou, “Silver Nanoparticle-Induced Oxidative Stress-Dependent Toxicity in Sprague-Dawley Rats,” Molecular and Cellular Biochemistry 399, no. 1–2 (2015): 257–268.

[44] E. O. Oisakede, O. O. Oyedeji, Olawuyi OF, J. O. Alabi, R. I. A. Daniel, and D. B. Olawade, “Nanoparticle-Mediated Cardiotoxicity and Nanomedicine Interventions in Cancer Treatment,” Nano TransMed 5 (2026): 100113.

[45] Y. Cong, R. Qiao, X. Wang, et al., “Protein Corona-Mediated Inhibition of Nanozyme Activity: Impact of Protein Shape,” Journal of the American Chemical Society 146, no. 15 (2024): 10478–10488.

[46] The benefits and risks of PEGylation in nanomedicine, “The Benefits and Risks of PEGylation in Nanomedicine,” Nature Nanotechnology 20, no. 5 (2025): 575.

[47] L. Jiao, H. Yan, Y. Wu, et al., “When Nanozymes Meet Single-Atom Catalysis,” Angewandte Chemie (International Ed. in English) 59, no. 7 (2020): 2565–2576.

[48] N. Kamaly, B. Yameen, J. Wu, and O. C. Farokhzad, “Degradable Controlled-Release Polymers and Polymeric Nanoparticles: Mechanisms of Controlling Drug Release,” Chemical Reviews 116, no. 4 (2016): 2602–2663.

[49] Q. Hu, Z. Huang, Y. Duan, Z. Fu, and L. Bin, “Reprogramming tumour Microenvironment With Photothermal Therapy,” Bioconjugate Chemistry 31, no. 5 (2020): 1268–1278.

[50] X. Shen, Z. Wang, X. J. Gao, and X. Gao, “Reaction Mechanisms and Kinetics of Nanozymes: Insights From Theory and Computation,” Advanced Materials 36, no. 10 (2024): e2211151.

[51] X. Zhuang, S. Gao, Y. Tao, M. Yuan, Z. Han, and Y. Wang, “pH-Responsive Nanozymes: Multifunctional Platforms for Biomedical Catalysis Toward Clinical Translation,” Frontiers in Bioengineering and Biotechnology 14 (2026): 1765647.

[52] Y. Hao, Y. Gao, Y. Fan, et al., “A tumour Microenvironment-Responsive Poly(Amidoamine) Dendrimer Nanoplatform for Hypoxia-Responsive Chemo/Chemodynamic Therapy,” Journal of Nanobiotechnology 20, no. 1 (2022): 43.

[53] C. Wu, D. Xu, M. Ge, et al., “Blocking Glutathione Regeneration: Inorganic NADPH Oxidase Nanozyme Catalyst Potentiates tumoural Ferroptosis,” Nano Today 46 (2022): 101574.

[54] P. Liu, L. Hao, M. Liu, and S. Hu, “Glutathione-Responsive and -Exhausting Metal Nanomedicines for Robust Synergistic Cancer Therapy,” Frontiers in Bioengineering and Biotechnology 11 (2023): 1161472.

[55] J. Fang, Y. Wang, Y. Jiang, T. Li, and X. Qiu, “Advances in Total Antioxidant Capacity Detection Based on Nanozyme,” Talanta 292 (2025): 127941.

[56] D. Xu, L. Wu, H. Yao, and L. Zhao, “Catalase-Like Nanozymes: Classification, Catalytic Mechanisms, and Their Applications,” Small 18, no. 37 (2022): e2203400.

[57] Y. Liao, Z. Zhang, Y. Zhao, et al., “Glucose Oxidase: An Emerging Multidimensional Treatment Option for Diabetic Wound Healing,” Bioactive Materials 44 (2025): 131–151.

[58] N. Singh, G. R. Sherin, and G. Mugesh, “Antioxidant and Prooxidant Nanozymes: From Cellular Redox Regulation to Next-Generation Therapeutics,” Angewandte Chemie (International Ed. in English) 62, no. 33 (2023): e202301232.

[59] N. M. Phan, T. L. Nguyen, and J. Kim, “Nanozyme-Based Enhanced Cancer Immunotherapy,” Tissue Engineering and Regenerative Medicine 19, no. 2 (2022): 237–252.

[60] S. Ning, Z. Zhang, Y. Ren, et al., “A Synergistic Dual-Atom Sites Nanozyme Augments Immunogenic Cell Death for Efficient Immunotherapy,” Advanced Science 12, no. 7 (2025): e2414734.

[61] W. Qiao, J. Chen, H. Zhou, et al., “A Single-Atom Manganese Nanozyme Mn-N/C Promotes Anti-tumour Immune Response via Eliciting Type I Interferon Signaling,” Advanced Science 11, no. 14 (2024): e2305979.

[62] P. Zhu, Y. Pu, M. Wang, W. Wu, H. Qin, and J. Shi, “MnOOH-Catalyzed Autoxidation of Glutathione for Reactive Oxygen Species Production and Nanocatalytic tumour Innate Immunotherapy,” Journal of the American Chemical Society 145, no. 10 (2023): 5803–5815.

[63] Y. Chen, Y. Chen, Z. Wang, et al., “Iron-Based MOF With Catalase-Like Activity Improves the Synergistic Therapeutic Effect of PDT/Ferroptosis/Starvation Therapy by Reversing the tumour Hypoxic Microenvironment,” Journal of Nanobiotechnology 22, no. 1 (2024): 705.

[64] A. Najafi, M. Keykhaee, H. Khorramdelazad, et al., “Catalase Application in Cancer Therapy: Simultaneous Focusing on Hypoxia Attenuation and Macrophage Reprogramming,” Biomedicine & Pharmacotherapy 153 (2022): 113483.

[65] W. Zeng, M. Yu, T. Chen, et al., “Polypyrrole Nanoenzymes as tumour Microenvironment Modulators to Reprogram Macrophage and Potentiate Immunotherapy,” Advanced Science 9, no. 23 (2022): e2201703.

[66] G. Hou, Y. Xu, C. Wang, et al., “Nanozyme-Based Strategies in Cancer Immunotherapy: Overcoming Resistance to Enhance Therapeutic Efficacy,” Aging and Disease 17, no. 1 (2025): 18–33.

[67] W. Yue, L. Chen, L. Yu, et al., “Checkpoint Blockade and Nanosonosensitizer-Augmented Noninvasive Sonodynamic Therapy Combination Reduces Tumour Growth and Metastases in Mice,” Nature Communications 10, no. 1 (2019): 2025.

[68] Z. Su, H. Xu, Y. Zhang, et al., “A Carbon Dot-Doped cu-MOF-Based Smart Nanoplatform for Enhanced Immune Checkpoint Blockade Therapy and Synergistic Multimodal Cancer Therapy,” Journal of Materials Chemistry B 11, no. 19 (2023): 4211–4226.

[69] T. N. Aslan and Ü. Ünüvar, “Green Fe₃O₄ Nanozymes for Cancer Detection, H₂O₂ Sensing and ROS-Mediated Apoptosis,” Microchemical Journal 213 (2025): 113643.

[70] M. Luo, F. K. Zhao, Y. M. Wang, and J. Bian, “Au@Pd Nanozyme-Mediated Catalytic Therapy: A Novel Strategy for Targeting tumour Microenvironment in Cancer Treatment,” Journal of Translational Medicine 22, no. 1 (2024): 814.

[71] Y. Xiao and D. Yu, “tumour Microenvironment as a Therapeutic Target in Cancer,” Pharmacology & Therapeutics 221 (2021): 107753.

[72] Y. Zhu, X. Yu, S. D. Thamphiwatana, Y. Zheng, and Z. Pang, “Nanomedicines Modulating tumour Immunosuppressive Cells to Enhance Cancer Immunotherapy,” Acta Pharmaceutica Sinica B 10, no. 11 (2020): 2054–2074.

[73] N. Nagarsheth, M. S. Wicha, and W. Zou, “Chemokines in the Cancer Microenvironment and Their Relevance in Cancer Immunotherapy,” Nature Reviews. Immunology 17, no. 9 (2017): 559–572.

[74] N. L. Syn, M. W. L. Teng, T. S. K. Mok, and R. A. Soo, “De-Novo and Acquired Resistance to Immune Checkpoint Targeting,” Lancet Oncology 18, no. 12 (2017): e731–e741.

[75] K. DePeaux and G. M. Delgoffe, “Metabolic Barriers to Cancer Immunotherapy,” Nature Reviews. Immunology 21, no. 12 (2021): 785–797.

[76] G. R. Khosravi, S. Mostafavi, S. Bastan, N. Ebrahimi, R. S. Gharibvand, and N. Eskandari, “Immunologic tumour Microenvironment Modulators for Turning Cold tumours Hot,” Cancer Commun (Lond) 44, no. 5 (2024): 521–553.

[77] A. D. Garg, S. Martin, J. Golab, and P. Agostinis, “Danger Signalling During Cancer Cell Death: Origins, Plasticity and Regulation,” Cell Death and Differentiation 21, no. 1 (2014): 26–38.

[78] S. S. Faria, S. Costantini, V. C. C. de Lima, et al., “NLRP3 Inflammasome-Mediated Cytokine Production and Pyroptosis Cell Death in Breast Cancer,” Journal of Biomedical Science 28, no. 1 (2021): 26.

[79] W. Qiao, C. Hu, J. Ma, et al., “Low-Dose Metronomic Chemotherapy Triggers Oxidized mtDNA Sensing Inside tumour Cells to Potentiate CD8(+)T Anti-tumour Immunity,” Cancer Letters 573 (2023): 216370.

[80] M. Tan, Z. Gao, X. Wang, et al., “MnO(2)@CeO(x)-GAMP Radiosensitizer With Oxygen Vacancies Depended Mimicking Enzyme-Like Activities for Radiosensitisation-Mediated STING Pathway Activation,” Biomaterials 314 (2025): 122797.

[81] C. Tang, H. Li, M. Sha, et al., “A tumour Microenvironment Responsive Titanium-Based Nanosonosensitizer for Combination Sonodynamic-Immunotherapy With Calcium Ion Overload,” Chemical Engineering Journal 475 (2023): 146054.

[82] H. Yang, G. Xu, F. Li, et al., “Multi-Enzyme Nanoparticles as Efficient Pyroptosis and Immunogenic Cell Death Inducers for Cancer Immunotherapy,” Advanced Science 11, no. 44 (2024): e2408729.

[83] X. Liu, Z. Liu, K. Dong, et al., “tumour-Activatable Ultrasmall Nanozyme Generator for Enhanced Penetration and Deep Catalytic Therapy,” Biomaterials 258 (2020): 120263.

[84] Q. Wang, Y. Yu, Y. Chang, et al., “Fluoropolymer-MOF Hybrids With Switchable Hydrophilicity for (19)F MRI-Monitored Cancer Therapy,” ACS Nano 17, no. 9 (2023): 8483–8498.

[85] S. Song, M. Yang, F. He, et al., “Multiple Therapeutic Mechanisms of Pyrrolic N-Rich g-C(3)N(4) Nanosheets With Enzyme-Like Function in the tumour Microenvironment,” Journal of Colloid and Interface Science 650, no. Pt B (2023): 1125–1137.

[86] W. Bian, X. Hu, R. Xiao, et al., “Catalytic Dual-Mode Immunotherapy: Anisotropic AuPt Heterostructure Decorated With Starry Pt Nanoclusters for Robust Cancer Photometalloimmunotherapy,” Advanced Science (Weinheim, Germany) 11, no. 28 (2024): e2403116.

[87] Z. He, Q. Wang, J. Du, et al., “Overcoming tumour Hypoxic Bismuth-Based Ternary Heterojunctions Enable Defect Modulation-Augmented tumour Sonocatalytic Immunotherapy,” Biomaterials 315 (2025): 122962.

[88] P. Hu, Y. Li, L. Zhang, et al., “Defect-Engineered Photothermal Nanozyme With NIR-II Absorption Induces Cuproptosis-Apoptosis for Synergized Cancer Immunotherapy and Fast Wound Healing,” Materials and Design 237 (2024): 112568.

[89] L. Huo, S. Zhu, J. Zeng, et al., “Multivalence Manganese Mediated Dual ROS Generator for Augmented Chemodynamic Therapy and Activated Antitumour Immunogenic Responses,” ACS Materials Letters 6, no. 3 (2024): 885–895.

[90] L. Louw, J. Steyl, and E. Loggenberg, “Imaging of Dual Ophthalmic Arteries: Identification of the Central Retinal Artery,” Journal of Clinical Imaging Science 4, no. 13 (2014): 40.

[91] Y. Xing, C. Yin, K. Luo, et al., “A High-Entropy Nanozyme-Based Photothermal-Adjuvant in Situ Nanovaccine for Potentiated tumour Immunotherapy,” Materials Chemistry Frontiers 9, no. 17 (2025): 2634–2645.

[92] H. Pan, X. Yu, Q. He, et al., “Vanadium Nitride Quantum Dots-Based Nanozyme in Synergy With Immune Checkpoint Blockade for Enhanced Cancer Immunotherapy Through Vanadate and Nitric Oxide,” Chemical Engineering Journal 514 (2025): 163245.

[93] R. Niu, B. Zhang, Y. Liu, et al., “Spatiotemporal Charging Single-Atom Nanozymes Activated Pyroptosis for Antitumour Immunotherapy via Bioorthogonal Disruption of Succination and Reinvigorating T Lymphocytes,” Advanced Materials 37, no. 33 (2025): e2502940.

[94] L. Zhao, X. Zhou, F. Xie, et al., “Ferroptosis in Cancer and Cancer Immunotherapy,” Cancer Commun (Lond) 42, no. 2 (2022): 88–116.

[95] H. Zhang, J. Lv, H. Wu, et al., “Endogenous/Exogenous Dual-Responsive Nanozyme for Photothermally Enhanced Ferroptosis-Immune Reciprocal Synergistic tumour Therapy,” Science Advances 11, no. 20 (2025): eadq3870.

[96] J. Liu, X. Shi, Y. Qu, and G. Wang, “Functionalized ZnMnFe(2)O(4)-PEG-FA Nanoenzymes Integrating Diagnosis and Therapy for Targeting Hepatic Carcinoma Guided by Multi-Modality Imaging,” Nanoscale 15, no. 26 (2023): 11013–11025.

[97] C. Deng, Z. Ye, C. J. Zheng, H. Cheng, and J. Ge, “Iron-Based Nanozymes Induced Ferroptosis for tumour Therapy,” Nanoscale 17, no. 23 (2025): 14103–14117.

[98] Z. Yi, X. Yang, Y. Liang, F. Chapelin, and S. Tong, “Enhancing ROS-Inducing Nanozyme Through Intraparticle Electron Transport,” Small 20, no. 6 (2024): e2305974.

[99] T. Bai, P. Xue, S. Shao, S. Yan, and X. Zeng, “Cholesterol Depletion-Enhanced Ferroptosis and Immunotherapy via Engineered Nanozyme,” Advanced Science 11, no. 38 (2024): e2405826.

[100] Y. Zhu, W. Wang, P. Gong, et al., “Enhancing Catalytic Activity of a Nickel Single Atom Enzyme by Polynary Heteroatom Doping for Ferroptosis-Based tumour Therapy,” ACS Nano 17, no. 3 (2023): 3064–3076.

[101] K. Xu, M. Chang, Z. Wang, et al., “Multienzyme-Mimicking LaCoO(3) Nanotrigger for Programming Cancer-Cell Pyroptosis,” Advanced Materials 35, no. 35 (2023): e2302961.

[102] M. R. Chiang, C. W. Hsu, W. C. Pan, et al., “Reprogramming Dysfunctional Dendritic Cells by a Versatile Catalytic Dual Oxide Antigen-Captured Nanosponge for Remotely Enhancing Lung Metastasis Immunotherapy,” ACS Nano 19, no. 2 (2025): 2117–2135.

[103] Y. Liu, R. Niu, R. Deng, S. Song, Y. Wang, and H. Zhang, “Multi-Enzyme co-Expressed Dual-Atom Nanozymes Induce Cascade Immunogenic Ferroptosis via Activating Interferon-Gamma and Targeting Arachidonic Acid Metabolism,” Journal of the American Chemical Society 145, no. 16 (2023): 8965–8978.

[104] K. Li, C. Lin, M. Li, et al., “Multienzyme-Like Reactivity Cooperatively Impairs Glutathione Peroxidase 4 and Ferroptosis Suppressor Protein 1 Pathways in Triple-Negative Breast Cancer for Sensitized Ferroptosis Therapy,” ACS Nano 16, no. 2 (2022): 2381–2398.

[105] C. Yao, R. Zhang, Z. Xie, Y. Wu, and X. Wu, “A Magnetically Actuated MOF-Based Nanozyme for Intensified Induction of Ferroptosis and Immunogenic Cell Death via Autophagy Blockade,” Small 21, no. 5 (2025): e2409026.

[106] C. Hao, L. Huang, H. Zhang, et al., “Chiral CuxOS@Fe-MOFs for Enhanced Cancer Therapy,” Advanced Functional Materials 34, no. 10 (2023): 2312795.

[107] H. Cai, P. Xue, Y. Ma, et al., “Cu-Based Hybrid Nanozyme for AMPK Activation and Enhanced PD-1 Checkpoint Blockade in Bladder Cancer Therapy,” Chemical Engineering Journal 517 (2025): 164343.

[108] T. Chen, C. Huang, Y. Liu, D. Nie, and J. Chen, “Bimetallic Nanozyme-Mediated Dual Ferroptosis/Cuproptosis Synergy Potentiates Immunotherapy in Bladder Cancer,” Colloids and Surfaces. B, Biointerfaces 255 (2025): 114954.

[109] Q. Wen, J. Liu, R. Kang, B. Zhou, and D. Tang, “The Release and Activity of HMGB1 in Ferroptosis,” Biochemical and Biophysical Research Communications 510, no. 2 (2019): 278–283.

[110] P. Wu, J. Chen, H. Li, H. Lu, Y. Li, and J. Zhang, “Interactions Between Ferroptosis and Tumour Development Mechanisms: Implications for Gynaecological Cancer Therapy (Review),” Oncology Reports 53, no. 2 (2025): 18.

[111] B. Farhood, M. Najafi, and K. Mortezaee, “CD8(+) Cytotoxic T Lymphocytes in Cancer Immunotherapy: A Review,” Journal of Cellular Physiology 234, no. 6 (2019): 8509–8521.

[112] E. Dai, L. Han, J. Liu, et al., “Autophagy-Dependent Ferroptosis Drives tumour-Associated Macrophage Polarization via Release and Uptake of Oncogenic KRAS Protein,” Autophagy 16, no. 11 (2020): 2069–2083.

[113] Z. F. Wen, H. Liu, R. Gao, et al., “tumour Cell-Released Autophagosomes (TRAPs) Promote Immunosuppression Through Induction of M2-Like Macrophages With Increased Expression of PD-L1,” Journal for Immunotherapy of Cancer 6, no. 1 (2018): 151.

[114] J. Yan, Y. Zeng, Z. Guan, et al., “Inherent Preference for Polyunsaturated Fatty Acids Instigates Ferroptosis of Treg Cells That Aggravates High-Fat-Diet-Related Colitis,” Cell Reports 43, no. 8 (2024): 114636.

[115] J. X. Shi, Z. C. Zhang, H. Z. Yin, et al., “RNA m6A Modification in Ferroptosis: Implications for Advancing tumour Immunotherapy,” Molecular Cancer 23, no. 1 (2024): 213.

[116] Z. Fan, S. Wu, H. Deng, G. Li, L. Huang, and H. Liu, “Light-Triggered Nanozymes Remodel the tumour Hypoxic and Immunosuppressive Microenvironment for Ferroptosis-Enhanced Antitumour Immunity,” ACS Nano 18, no. 19 (2024): 12261–12275.

[117] L. Yao, M. M. Zhao, Q. W. Luo, et al., “Carbon Quantum Dots-Based Nanozyme From Coffee Induces Cancer Cell Ferroptosis to Activate Antitumour Immunity,” ACS Nano 16, no. 6 (2022): 9228–9239.

[118] S. M. Wearne, T. Dornan, P. W. Teunissen, and T. Skinner, “Supervisor Continuity or Co-Location: Which Matters in Residency Education? Findings From a Qualitative Study of Remote Supervisor Family Physicians in Australia and Canada,” Academic Medicine 90, no. 4 (2015): 525–531.

[119] L. Yang, M. Pan, H. Hu, et al., “Bioinspired Bimetallic Ions Functionalized MOF SAzyme Nanocomposites for Synergistic Ferroptosis/Cuproptosis-Enhanced Immune Checkpoint Therapy,” bioRxiv – Bioengineering (2024): 2024.08.12.607118.

[120] Q. Hao, Y. Gan, and X. Zhou, “Tackling Cuproptosis: From Metabolic Rewiring to Therapeutic Exploitation in Cancer,” Cellular & Molecular Immunology 23, no. 3 (2026): 239–260.

[121] L. J. Yang, M. M. Pan, H. Hu, et al., “Bioinspired Dual-Ionic-Site Single-Atom Nanozymes for Synergistic Ferroptosis/Cuproptosis and Enhanced Immune Checkpoint Blockade Therapy,” Small 21, no. 35 (2025): e2501076.

[122] L. Gu, Y. Sun, T. Bai, et al., “Functional Nanozyme System for Synergistic tumour Immunotherapy via Cuproptosis and Ferroptosis Activation,” Journal of Nanobiotechnology 23, no. 1 (2025): 212.

[123] Q. Wu, L. You, E. Nepovimova, et al., “Hypoxia-Inducible Factors: Master Regulators of Hypoxic tumour Immune Escape,” Journal of Hematology & Oncology 15, no. 1 (2022): 77.

[124] C. M. Huo, P. L. Ding, S. Y. Tong, et al., “Biomimetic Nanozymes Catalyze Cascade Reactions for Enhanced tumour Nanocatalytic Therapy,” Nanoscale Horizons 10, no. 10 (2025): 2381–2396.

[125] B. Xu, Y. Cui, W. Wang, et al., “Immunomodulation-Enhanced Nanozyme-Based tumour Catalytic Therapy,” Advanced Materials 32, no. 33 (2020): e2003563.

[126] B. Zhang, Y. Yuan, Q. Xin, et al., “Self-Oxygenated Biomimetic Nanozyme for tumour Catalytic Immunotherapy,” Advanced Functional Materials 35, no. 1 (2024): 2411103.

[127] C. Wang, Y. Li, W. Yang, L. Zhou, and S. Wei, “Nanozyme With Robust Catalase Activity by Multiple Mechanisms and Its Application for Hypoxic tumour Treatment,” Advanced Healthcare Materials 10, no. 19 (2021): e2100601.

[128] Y. Guo, X. Gao, F. He, et al., “AuPt-Loaded Fe-N-C Flower-Like Nanocascade Reactor With Self-Supplied Reaction Substrates and Multiple Enzyme Activities for the Study of Hypoxic tumours,” Biomaterials Advances 176 (2025): 214341.

[129] X. Lei, J. Meng, T. Gao, et al., “pH-Responsive Photothermal Effect and Heterojunction Formation for tumour-Specific Pyroelectrodynamic and Nanozyme-Catalyzed Starvation Therapy,” Acta Biomaterialia 197 (2025): 444–459.

[130] J. Liu, M. Wang, X. Yang, et al., “Covalent Conjugation of Doxorubicin to Polydopamine on the Surface of Single-Atom Nanozyme for Effective Synergistic Cancer Therapy,” Science China: Chemistry 68, no. 8 (2025): 3852–3867.

[131] F. Wu, H. Chen, R. Liu, et al., “Modulation of the tumour Immune Microenvironment by bi(2) Te(3) -Au/Pd-Based Theranostic Nanocatalysts Enables Efficient Cancer Therapy,” Advanced Healthcare Materials 11, no. 19 (2022): e2200809.

[132] S. Li, L. Shang, B. Xu, et al., “A Nanozyme With Photo-Enhanced Dual Enzyme-Like Activities for Deep Pancreatic Cancer Therapy,” Angewandte Chemie (International Ed. in English) 58, no. 36 (2019): 12624–12631.

[133] H. Mao, Y. Wen, Y. Yu, H. Li, J. Wang, and B. Sun, “Bioinspired Nanocatalytic tumour Therapy by Simultaneous Reactive Oxygen Species Generation Enhancement and Glutamine Pathway-Mediated Glutathione Depletion,” Journal of Materials Chemistry B 11, no. 1 (2022): 131–143.

[134] O. R. Colegio, N. Q. Chu, A. L. Szabo, et al., “Functional Polarization of Tumour-Associated Macrophages by Tumour-Derived Lactic Acid,” Nature 513, no. 7519 (2014): 559–563.

[135] L. Zhang and S. Li, “Lactic Acid Promotes Macrophage Polarization Through MCT-HIF1alpha Signaling in Gastric Cancer,” Experimental Cell Research 388, no. 2 (2020): 111846.

[136] H. Kanemaru, Y. Mizukami, A. Kaneko, et al., “A Mechanism of Cooling Hot tumours: Lactate Attenuates Inflammation in Dendritic Cells,” iScience 24, no. 9 (2021): 103067.

[137] K. Yang, J. Xu, M. Fan, et al., “Lactate Suppresses Macrophage Pro-Inflammatory Response to LPS Stimulation by Inhibition of YAP and NF-kappaB Activation via GPR81-Mediated Signaling,” Frontiers in Immunology 11 (2020): 587913.

[138] D. Zhang, Z. Tang, H. Huang, et al., “Metabolic Regulation of Gene Expression by Histone Lactylation,” Nature 574, no. 7779 (2019): 575–580.

[139] K. Renner, C. Bruss, A. Schnell, et al., “Restricting Glycolysis Preserves T Cell Effector Functions and Augments Checkpoint Therapy,” Cell Reports 29, no. 1 (2019): 135–150 e139.

[140] S. Kumagai, S. Koyama, K. Itahashi, et al., “Lactic Acid Promotes PD-1 Expression in Regulatory T Cells in Highly Glycolytic tumour Microenvironments,” Cancer Cell 40, no. 2 (2022): 201–218 e209.

[141] J. Gu, J. Zhou, Q. Chen, et al., “tumour Metabolite Lactate Promotes tumourigenesis by Modulating MOESIN Lactylation and Enhancing TGF-Beta Signaling in Regulatory T Cells,” Cell Reports 39, no. 12 (2022): 110986.

[142] S. Wu, L. Xu, C. He, et al., “Lactate Efflux Inhibition by Syrosingopine/LOD co-Loaded Nanozyme for Synergetic Self-Replenishing Catalytic Cancer Therapy and Immune Microenvironment Remodeling,” Advanced Science 10, no. 26 (2023): e2300686.

[143] W. Zou, F. Gao, Z. Meng, et al., “Lactic Acid Responsive Sequential Production of Hydrogen Peroxide and Consumption of Glutathione for Enhanced Ferroptosis tumour Therapy,” Journal of Colloid and Interface Science 663 (2024): 787–800.

[144] W. Sun, J. Song, C. Zhu, et al., “Multienzymatic Hybrid Metalloenzymes Triggering Cascade Reactions-Regulated tumour Redox Homeostasis and Immunosuppressive Microenvironment for Catalytic Immunotherapy,” ACS Nano 19, no. 26 (2025): 24034–24051.

[145] Y. Fu, Y. Zhang, Y. Zhang, et al., “Nanoreactors With Cascade Catalytic Activity Reprogram the tumour Microenvironment for Enhanced Immunotherapy by Synchronously Regulating Treg and Macrophage Cells,” ACS Applied Materials & Interfaces 16, no. 37 (2024): 49053–49068.

[146] R. Dou, L. Wang, J. Zhang, et al., “Reversing Photodynamic Therapy-Induced tumour Metabolic Symbiosis and Immune Evasion Delivers a Two-Punch Attack on tumours,” Small 21, no. 11 (2025): e2409052.

[147] J. Zhang, Y. Pan, L. Liu, et al., “Genetically Edited Cascade Nanozymes for Cancer Immunotherapy,” ACS Nano 18, no. 19 (2024): 12295–12310.

[148] R. Tao, J. Cai, H. Duan, Y. Hua, B. Geng, and J. Qin, “Biodegradable MnO2-x Sensitized Hollow Prussian Blue for Enhanced Sono-Immunotherapy Through Cascade Amplification of ROS Generation and Activation of cGAS-STING Pathway,” Chemical Engineering Journal 519 (2025): 165530.

[149] Z. Chen, Q. He, R. Qian, et al., “Reengineering the tumour Oxygen Microenvironment in Radiotherapy to Enhance T-Cell Function for Radio-Immunotherapy,” Advanced Functional Materials 35, no. 38 (2025): 2502807.

[150] C. Qu, X. Y. Shao, R. Jia, et al., “Hypoxia Reversion and STING Pathway Activation Through Large Mesoporous Nanozyme for Near-Infrared-II Light Amplified tumour Polymetallic-Immunotherapy,” ACS Nano 18, no. 33 (2024): 22153–22171.

[151] M. Wang, M. Chang, P. Zheng, et al., “A Noble AuPtAg-GOx Nanozyme for Synergistic tumour Immunotherapy Induced by Starvation Therapy-Augmented Mild Photothermal Therapy,” Advanced Science 9, no. 31 (2022): e2202332.

[152] Z. Zhou, J. Huang, Z. Zhang, et al., “Bimetallic PdPt-Based Nanocatalysts for Photothermal-Augmented tumour Starvation and Sonodynamic Therapy in NIR-II Biowindow Assisted by an Oxygen Self-Supply Strategy,” Chemical Engineering Journal 435 (2022): 135085.

[153] K. Guo, H. Liu, M. Zhang, et al., “Overcoming Radiation-Induced PD-L1 Upregulation by Novel Gadolinium-Palladium Nanoplatforms for Enhanced tumour Radio-Immunotherapy,” Chemical Engineering Journal 504 (2025): 158754.

[154] K. Kang, L. Wang, K. Yu, Y. Ma, F. Qu, and H. Lin, “Z-Scheme MoS(2)/co(3)S(4)@PEG Nanoflowers: Intracellular NIR-II Photocatalytic O(2) Production Facilitating Hypoxic tumour Therapy,” Biomaterials Advances 144 (2023): 213168.

[155] Q. Xu, S. Li, M. Qiu, et al., “A Bimodal MRI-Traceable Nanozyme With Immune-Activated Capability for Immunotherapy of Lung Metastases,” ACS Applied Bio Materials 8, no. 7 (2025): 5818–5829.

[156] K. Zhu, Z. Wu, Q. Li, et al., “Immune Microenvironment-Reshaping au@Bi2Te3 Nanoparticles for Spectral Computed Tomography/Photoacoustic Imaging-Guided Synergetic Photo/Radio/Immunotherapy,” Nano Research 16, no. 1 (2022): 771–781.

[157] L. Menilli, C. Milani, E. Martella, et al., “Paclitaxel and Nlg919 co-Loaded MnO2–Albumin Nanoparticles for Synergistic Chemoimmune Cancer Therapy,” ACS Applied Nano Materials 8, no. 9 (2025): 4911–4925.

[158] H. Wang, B. Wang, J. Jiang, et al., “SnSe Nanosheets Mimic Lactate Dehydrogenase to Reverse tumour Acid Microenvironment Metabolism for Enhancement of tumour Therapy,” Molecules 27, no. 23 (2022): 8552.

[159] M. Ma, Y. Zhang, K. Pu, and W. Tang, “Nanomaterial-Enabled Metabolic Reprogramming Strategies for Boosting Antitumour Immunity,” Chemical Society Reviews 54, no. 2 (2025): 653–714.

[160] Y. Xie, M. Wang, L. Qiao, et al., “Photothermal-Enhanced Dual Inhibition of Lactate/Kynurenine Metabolism for Promoting tumour Immunotherapy,” Small Methods 8, no. 3 (2024): e2300945.

[161] Z. Li, B. Zhang, S. Duan, et al., “Ultrasound-Activated Nanovesicles for Adenosine Exhaustion and Immune Checkpoint Blockade in Cancer Immunotherapy,” Journal of Controlled Release 385 (2025): 113988.

[162] C. Cong, C. Li, G. Cao, et al., “Dual-Activity Nanozyme to Initiate Tandem Catalysis for Doubly Enhancing ATP-Depletion Anti-tumour Therapy,” Biomaterials Advances 143 (2022): 213181.

[163] L. Qiao, G. Zhu, T. Jiang, et al., “Self-Destructive Copper Carriers Induce Pyroptosis and Cuproptosis for Efficient tumour Immunotherapy Against Dormant and Recurrent tumours,” Advanced Materials 36, no. 8 (2024): e2308241.

[164] X. K. Jin, S. K. Zhang, S. M. Zhang, et al., “Disrupting Intracellular Homeostasis by Copper-Based Nanoinducer With Multiple Enzyme-Mimicking Activities to Induce Disulfidptosis-Enhanced Pyroptosis for tumour Immunotherapy,” Advanced Materials 37, no. 1 (2025): e2410957.

[165] X. Zhao, S. Yao, X. Wan, et al., “Immunostimulatory Multi-Interfacial Bimetallic Phosphide Nanoparticles as Photo-Enhanced Cascade Nanozyme for Cancer Therapy,” Applied Materials Today 25 (2021): 101255.

[166] Y. Liu, R. Niu, H. Zhao, et al., “Single-Site Nanozymes With a Highly Conjugated Coordination Structure for Antitumour Immunotherapy via Cuproptosis and Cascade-Enhanced T Lymphocyte Activity,” Journal of the American Chemical Society 146, no. 6 (2024): 3675–3688.

[167] H. He, L. Du, H. Xue, et al., “Triple tumour Microenvironment-Responsive Ferroptosis Pathways Induced by Manganese-Based Imageable Nanoenzymes for Enhanced Breast Cancer Theranostics,” Small Methods 7, no. 7 (2023): e2300230.

[168] M. Chang, Z. Hou, D. Jin, et al., “Colorectal tumour Microenvironment-Activated Bio-Decomposable and Metabolizable Cu₂O@CaCO₃ Nanocomposites for Synergistic Oncotherapy,” Advanced Materials 32, no. 43 (2020): e2004647.

[169] J. Yang, L. Fang, R. Jiang, et al., “RuCu Nanosheets With Ultrahigh Nanozyme Activity for Chemodynamic Therapy,” Advanced Healthcare Materials 12, no. 23 (2023): e2300490.

[170] D. Nie, Y. Ling, W. Lv, et al., “In Situ Attached Photothermal Immunomodulation-Enhanced Nanozyme for the Inhibition of Postoperative Malignant Glioma Recurrence,” ACS Nano 17, no. 14 (2023): 13885–13902.

[171] J. Li, C. Cao, X. Zhang, X. Zhang, and S. Wang, “Bifunctional Cascaded Single-Atom Nanozymes for Enhanced Photodynamic Immunotherapy Through Dual-Depressing PD-L1 and Regulating Hypoxia,” Biomaterials 317 (2025): 123106.

[172] H. Kamli and N. U. Khan, “Revolutionising Cancer Intervention: The Repercussions of CAR-T Cell Therapy on Modern Oncology Practices,” Medical Oncology 42, no. 7 (2025): 228.

[173] J. He, W. Xue, and Y. Li, “tumour Microenvironment-Responsive Nanomedicine: Monitoring and Modulating the tumour Microenvironment for Precision Cancer Therapy,” International Journal of Nanomedicine 21 (2026): 560983.

[174] X. Cai, R. Liu, H. Yan, et al., “Cascaded Nanozyme With in Situ Enhanced Photothermal Capacity for tumour-Specific and Self-Replenishing Cancer Therapy,” Advanced Healthcare Materials 12, no. 27 (2023): e2300516.

[175] J. H. Feng, M. L. Zhang, Y. M. Zou, et al., “Hollow Gold-Platinum Nanoshells as a Delivery Platform for Ce6: Cascading Catalysis for Enhanced Multimodal Therapy in tumour Ablation and Antitumour Immunity,” Nanoscale 17, no. 9 (2025): 5456–5471.

[176] T. Wang, F. Zhang, C. F. Guimarães, et al., “Zn/cu bi-Single-Atom Nanoplatform: Hexagonal Anti-tumour Warrior by ROS Amplification for DOX Resistance Reversal and Immune Activation,” Advanced Functional Materials 34, no. 52 (2024): 2410962.

[177] H. Cui, X. Zhang, Z. Zhang, et al., “Killing Three Birds With One Stone: tumour-Membrane-Decorated Prussian Blue Nanovaccines for Synergistic Management of Skin tumours, Radiation Dermatitis and Wounds,” Composites Part B: Engineering 264 (2023): 110900.

[178] H. He, Z. Fei, T. Guo, et al., “Bioadhesive Injectable Hydrogel With Phenolic Carbon Quantum Dot Supported Pd Single Atom Nanozymes as a Localized Immunomodulation Niche for Cancer Catalytic Immunotherapy,” Biomaterials 280 (2022): 121272.

[179] D. M. Pardoll, “The Blockade of Immune Checkpoints in Cancer Immunotherapy,” Nature Reviews. Cancer 12, no. 4 (2012): 252–264.

[180] X. He and C. Xu, “Immune Checkpoint Signaling and Cancer Immunotherapy,” Cell Research 30, no. 8 (2020): 660–669.

[181] A. Ribas and J. D. Wolchok, “Cancer Immunotherapy Using Checkpoint Blockade,” Science 359, no. 6382 (2018): 1350–1355.

[182] J. Larkin, V. Chiarion-Sileni, R. Gonzalez, et al., “Five-Year Survival With Combined Nivolumab and Ipilimumab in Advanced Melanoma,” New England Journal of Medicine 381, no. 16 (2019): 1535–1546.

[183] P. Ouyang, L. Wang, J. Wu, et al., “Overcoming Cold tumours: A Combination Strategy of Immune Checkpoint Inhibitors,” Frontiers in Immunology 15 (2024): 1344272.

[184] M. Suo, D. Yang, M. Yang, et al., “Biomimetic Organic Nanozyme as tumour Vaccines for Targeted Suppression of Ammonia-Induced T Lymphocyte Death to Augment Breast Cancer Immunotherapy,” Advanced Science 13, no. 11 (2026): e18037.

[185] W. Sun, C. Zhu, J. Song, et al., “Hydrogen Sulfide Gas Amplified ROS Cascade: FeS@GOx Hybrid Nanozyme Designed for Boosting tumour Chemodynamic Immunotherapy,” Advanced Healthcare Materials 12, no. 23 (2023): e2300385.

[186] C. Hu, R. Man, H. Li, M. Xia, Z. Yu, and B. Tang, “Near-Infrared Triggered Self-Accelerating Nanozyme Camouflaged With a Cancer Cell Membrane for Precise Targeted Imaging and Enhanced Cancer Immunotherapy,” Analytical Chemistry 95, no. 36 (2023): 13575–13585.

[187] G. Hou, J. Qian, M. Guo, et al., “Copper Coordinated Nanozyme-Assisted Photodynamic Therapy for Potentiating PD-1 Blockade Through Amplifying Oxidative Stress,” Chemical Engineering Journal 435 (2022): 134778.

[188] Y. Li, J. Huang, H. Yu, et al., “Zirconia-Platinum Nanohybrids for Ultrasound-Activated Sonodynamic-Thermodynamic Bimodal Therapy by Inducing Intense Intracellular Oxidative Stress,” Small 18, no. 38 (2022): e2203080.

[189] M. Cao, Y. Liu, Z. Zhang, et al., “Hollow RuO(2) Nanozymes Sensitized by Carbon Dot Sonosensitizers for Sonodynamic/Chemodynamic-Activated Immunotherapy,” Theranostics 16, no. 5 (2026): 2357–2371.

[190] Y. Li, L. Wang, K. Kang, et al., “All in One Theranostic Nanoagent Based on MoSe2/au@PEG Hollow Nanospheres for the Enhanced Synergetic Antitumour,” Chemical Engineering Journal 429 (2022): 132330.

[191] M. Wang, S. Choi, Q. Bai, et al., “Hollow co-CeO2@PEG Nanospheres: Ultrasound Enhanced Cascade-Nanozyme for Synergetic Anticancer,” Chemical Engineering Journal 456 (2023): 140993.

[192] Y. Xiao, F. Lai, M. Xu, et al., “Dual-Functional Nanoplatform Based on Bimetallic Metal-Organic Frameworks for Synergistic Starvation and Chemodynamic Therapy,” ACS Biomaterials Science & Engineering 9, no. 4 (2023): 1991–2000.

[193] D. Zhang, X. Cai, Y. Li, et al., “Nanozyme With Dual Enzyme Activity Mediating Cascade Catalytic Therapy Synergize Multiple Functions for Antitumour Therapy,” Chinese Chemical Letters 37, no. 3 (2026): 111569.

[194] K. Luo, S. You, J. Chen, et al., “Construction of Multifunctional Nanozymes With Amplified Immunogenic Death Effect as a Long-Term Anti-tumour Nanoplatform,” Biomaterials Advances 175 (2025): 214336.

[195] Y. Ren, F. Wu, L. Huo, et al., “Switchable ROS Generator and Scavenger to Prevent the Cisplatin Induced Acute Kidney Injury and Improve Efficacy via Synergistic Chemodynamic/Immune Therapy,” Materials Today Bio 29 (2024): 101328.

[196] R. Wang, M. Qiu, L. Zhang, et al., “Augmenting Immunotherapy via Bioinspired MOF-Based ROS Homeostasis Disruptor With Nanozyme-Cascade Reaction,” Advanced Materials 35, no. 49 (2023): e2306748.

[197] Z. Wang, T. Sha, J. Li, et al., “Turning Foes to Friends: Advanced “In Situ Nanovaccine” With Dual Immunoregulation for Enhanced Immunotherapy of Metastatic Triple-Negative Breast Cancer,” Bioactive Materials 39 (2024): 612–629.

[198] Y. Xie, M. Wang, Y. Qian, et al., “Novel PdPtCu Nanozymes for Reprogramming tumour Microenvironment to Boost Immunotherapy Through Endoplasmic Reticulum Stress and Blocking IDO-Mediated Immune Escape,” Small 19, no. 44 (2023): e2303596.

[199] Y. Yin, H. Wang, J. Xue, C. Yin, Y. Xing, and W. Gu, “Immuno-Nanozymes Mediated Synergistic Chemodynamic/Immuno-Therapy With Potentiated Anti-tumour Efficacy,” Advanced Healthcare Materials 12, no. 29 (2023): e2301269.

[200] Q. Ding, H. Liu, L. Yan, et al., “Engineering a Multifunctional Nanozyme Platform for Synergistic Melanoma Therapy: Integrating Enzyme Activity, Immune Activation, and Low-Temperature Photothermal Effects,” Angewandte Chemie (International Ed. in English) 64, no. 32 (2025): e202505911.

[201] L.-S. Li, W.-Q. Zhu, B.-B. Liu, et al., “In Situ Disulfiram Toxification Synergizes au–Pt Nanozymes to Amplify Cuproptosis to Enhance Hepatocellular Carcinoma Chemotherapy and Immunotherapy,” Materials Today Chemistry 47 (2025): 102877.

[202] Y. Zhang, Y. Yang, J. Shi, and L. Wang, “A Multimodal Strategy of Fe(3)O(4)@ZIF-8/GOx@MnO(2) Hybrid Nanozyme via TME Modulation for tumour Therapy,” Nanoscale 13, no. 39 (2021): 16571–16588.

[203] L. Zhao, J. Ji, N. Wang, et al., “MXene-Based Nanozymes Remodel tumour Microenvironment for Heterojunction-Enhanced Sonodynamic and Chemodynamic Therapy to Boost Robust Cancer Immunotherapy,” Chemical Engineering Journal 500 (2024): 156730.

[204] Y. Cai, T. Chai, W. Nguyen, et al., “Phototherapy in Cancer Treatment: Strategies and Challenges,” Signal Transduction and Targeted Therapy 10, no. 1 (2025): 115.

[205] J. Wang, M. Liu, J. Wang, et al., “Zinc Oxide Nanoparticles With Catalase-Like Nanozyme Activity and Near-Infrared Light Response: A Combination of Effective Photodynamic Therapy, Autophagy, Ferroptosis, and Antitumour Immunity,” Acta Pharmaceutica Sinica B 14, no. 10 (2024): 4493–4508.

[206] S. Wei, Y. Yuan, W. Xie, et al., “Ion-Engineered Clay Nanozyme via tumour Microenvironment Remodeling for Enhanced tumour Therapy,” Small 20, no. 51 (2024): e2402648.

[207] A. E. Chuang, Y. K. Tao, S. W. Dong, H. T. Nguyen, and C. H. Liu, “Polypyrrole/Iron-Glycol Chitosan Nanozymes Mediate M1 Macrophages to Enhance the X-Ray-Triggered Photodynamic Therapy for Bladder Cancer by Promoting Antitumour Immunity,” International Journal of Biological Macromolecules 280, no. Pt 4 (2024): 135608.

[208] B. Li, D. Xu, Y. Chen, et al., “Polyethylenimine-Coated Pt–Mn Nanostructures for Synergistic Photodynamic/Photothermal/Chemodynamic tumour Therapy,” ACS Applied Nano Materials 7, no. 8 (2024): 9428–9440.

[209] M. Xu, R. Zhao, B. Liu, et al., “Ultrasmall Copper-Based Nanoplatforms for NIR-II Light-Triggered Photothermal/Photodynamic and Amplified Nanozyme Catalytic Therapy of Hypoxic tumour,” Chemical Engineering Journal 491 (2024): 151776.

[210] Z. Zeng, C. Zhang, J. Li, D. Cui, Y. Jiang, and K. Pu, “Activatable Polymer Nanoenzymes for Photodynamic Immunometabolic Cancer Therapy,” Advanced Materials 33, no. 4 (2021): e2007247.

[211] Y. Cao, T. Wu, W. Dai, H. Dong, and X. Zhang, “TiO2 Nanosheets With the au Nanocrystal-Decorated Edge for Mitochondria-Targeting Enhanced Sonodynamic Therapy,” Chemistry of Materials 31, no. 21 (2019): 9105–9114.

[212] X. Chang, Q. Wu, Y. Wu, et al., “Multifunctional au Modified Ti(3)C(2)-MXene for Photothermal/Enzyme Dynamic/Immune Synergistic Therapy,” Nano Letters 22, no. 20 (2022): 8321–8330.

[213] X. Qian, R. Shi, J. Chen, et al., “The Single-Atom Iron Nanozyme Mimicking Peroxidase Remodels Energy Metabolism and tumour Immune Landscape for Synergistic Chemodynamic Therapy and Photothermal Therapy of Triple-Negative Breast Cancer,” Frontiers in Bioengineering and Biotechnology 10 (2022): 1026761.

[214] Q. Wang, D. Niu, J. Shi, and L. Wang, “A Three-In-One ZIFs-Derived CuCo(O)/GOx@PCNs Hybrid Cascade Nanozyme for Immunotherapy/Enhanced Starvation/Photothermal Therapy,” ACS Applied Materials & Interfaces 13, no. 10 (2021): 11683–11695.

[215] R. Thakur and R. Goyal, “Tinea Capitis: Mixed or Consecutive Infection With White and Violet Strains of Trichophyton Violaceum: A Diagnostic or Therapeutic Challenge,” Journal of Clinical and Diagnostic Research 9, no. 12 (2015): WD03–WD04.

[216] H. Yu, Y. Huang, Z. Nong, et al., “In-Situ Grown Nanocrystal TiO(2) on 2D Ti(3)C(2) Nanosheets With Anti-tumour Activity From Photo-Sonodynamic Treatment and Immunology,” International Journal of Nanomedicine 19 (2024): 7963–7981.

[217] H. Yu, X. Xu, X. Wang, et al., “Prussian-Blue-Functionalized Polypyrrole Nanozyme via PTEN Activation and Hypoxia Reversal for Enhanced Photothermal Therapy of tumour,” ACS Biomaterials Science & Engineering 11, no. 7 (2025): 4453–4467.

[218] G. Zhu, P. Zheng, M. Wang, et al., “Near-Infrared Light-Triggered Thermoresponsive Pyroptosis System for Synergistic tumour Immunotherapy,” Advanced Healthcare Materials 13, no. 4 (2024): e2302095.

[219] Y. Zhang, K. Wang, G. Xing, et al., “Nanozyme-Laden Intelligent Macrophage EXPRESS Amplifying Cancer Photothermal-Starvation Therapy by Responsive Stimulation,” Materials Today Bio 16 (2022): 100421.

[220] R. Mu, W. Song, Z. Li, et al., “Engineering the Electronic Structure of Fe-MoO(2)@PEG to Increase Sonodynamic and Multi-Nanozyme Activities for Anticancer Therapy,” Journal of Colloid and Interface Science 701 (2026): 138626.

[221] H. Qu, Y. Zhang, M. Chen, et al., “NIR-II Photo- and Sono-Responsive Hyaluronic Acid-Capped Nanozymes for Glioblastoma-Targeting Theranostics,” International Journal of Biological Macromolecules 306, no. Pt 3 (2025): 141737.

[222] W. Wang, R. Jia, F. Qu, and H. Lin, “Defect-Rich Ni-CoO@PEG Porous Hexagonal Nanosheets: Multi-Enzyme and Ultrasound Catalysis for Synergistic Anticancer Treatment,” ACS Applied Materials & Interfaces 15, no. 11 (2023): 13917–13928.

[223] N. Tao, H. Li, L. Deng, et al., “A Cascade Nanozyme With Amplified Sonodynamic Therapeutic Effects Through Comodulation of Hypoxia and Immunosuppression Against Cancer,” ACS Nano 16, no. 1 (2022): 485–501.

[224] X.-X. Chen, Q.-H. Shen, X.-Y. Rao, P. Wang, and C.-P. Tan, “Carbon Dots-Mediated Lysosomal Iron Sequestration for Cancer Immunostimulation,” Chemical Engineering Journal 520 (2025): 166201.

[225] Q. Jiang, B. Qiao, X. Lin, et al., “A Hydrogen Peroxide Economizer for On-Demand Oxygen Production-Assisted Robust Sonodynamic Immunotherapy,” Theranostics 12, no. 1 (2022): 59–75.

[226] M. Cui, L. Qian, K. Lu, et al., “Defect-Rich Metastable MoS(2) Promotes Macrophage Reprogramming in Breast Cancer: A Clinical Perspective,” Small 20, no. 43 (2024): e2402101.

[227] W. Lv, G. Jiang, X. Lin, et al., “An Unusual Application of Multifunctional Nanozyme Derived From COF: Augmenting Chemoimmunotherapy While Attenuating Cardiotoxicity,” Advanced Functional Materials 35, no. 2 (2024): 2412862.

[228] D. Miao, R. Luo, Y. Li, et al., “Injectable Functional Porous Carbon-Loaded Hydrogel With Long-Term Retention and Synergistic Anti-tumour Properties for tumour Therapy,” Advanced Materials 37, no. 37 (2025): e2502455.

[229] W. Tang, X. Li, M. Lyu, and Q. Huang, “Cancer Cell Membrane Biomimetic Mesoporous Nanozyme System With Efficient ROS Generation for Antitumour Chemoresistance,” Oxidative Medicine and Cellular Longevity 2022 (2022): 5089857.

[230] Y. Su, H. Wu, K. Duan, et al., “Synergistic tumour Microenvironment Modulation Enabled by a Nanozyme-Boosted Biomimetic Macrophage-Derived Nanovesicle for Highly Efficient Antitumour Therapy,” Theranostics 15, no. 16 (2025): 7925–7939.

[231] P. Wang, W. Guo, S. Liu, et al., “Novel Pt@PCN-Cu-Induced Cuproptosis Amplifies alphaPD-L1 Immunotherapy in Pancreatic Ductal Adenocarcinoma Through Mitochondrial HK2-Mediated PD-L1 Upregulation,” Journal of Experimental & Clinical Cancer Research 44, no. 1 (2025): 149.

[232] C. Chen, M. Shen, X. Wan, et al., “Decoy Extracellular Vesicles Overcome Triple-Negative Breast Cancer Heterogeneity via Membrane-Cytoplasm-Mitochondria Cascade Targeting,” Advanced Science 12, no. 40 (2025): e07975.

[233] T. Fang, S. Ma, Y. Wei, J. Yang, J. Zhang, and Q. Shen, “Catalytic Immunotherapy-Photothermal Therapy Combination for Melanoma by Ferroptosis-Activating Vaccine Based on Artificial Nanoenzyme,” Materials Today Chemistry 27 (2023): 101308.

[234] X. Lu, Z. Chen, Y. Li, et al., “Ultrasmall AuCe Nanozyme Adjuvant Boosted ROS for Three-Pronged tumour Immunotherapy,” Nano Today 55 (2024): 102205.

[235] R. Wang, J. Li, X. Wang, et al., “Personalized Nanovaccines Enhance Lymph Node Accumulation and Reprogram the tumour Microenvironment for Improved Photodynamic Immunotherapy,” Nano Letters 24, no. 24 (2024): 7432–7442.

[236] Y. Sun, X. Yao, Y. Zhang, et al., “Zinc Oxide-Copper Sulfide Nanozyme Hydrogels for Bone Defect Repair by Modulating the Bone Immune Microenvironment and Promoting Osteogenesis/Angiogenesis,” ACS Applied Materials & Interfaces 17, no. 20 (2025): 29100–29118.

[237] M. Zhang, J. Zhou, X. Jiang, et al., “MoS2 Nanozyme–Chlorella Hydrogels: Pioneering a Hepatocellular Carcinoma Integrative Therapy,” Advanced Functional Materials 35, no. 12 (2025): 2417125.

[238] D. Zhu, H. Chen, C. Huang, et al., “H₂O₂ Self-Producing Single-Atom Nanozyme Hydrogels as Light-Controlled Oxidative Stress Amplifier for Enhanced Synergistic Therapy by Transforming “Cold” tumours,” Advanced Functional Materials 32, no. 16 (2022): 1616–3028.

[239] Y. Li, H. Feng, H. Yang, et al., “A Self-Priming Pyroptosis-Inducing Agent for Activating Anticancer Immunity,” Advanced Healthcare Materials 14, no. 11 (2025): 2500610.

[240] Y. Wu, Y. Zhang, J. Han, et al., “Nanozyme-Based Biomimetic Intelligent Immune Organelles for the Treatment of Bladder-Metastasized tumours,” Advanced Materials 37, no. 43 (2025): e11181.

[241] D. Zhu, R. Ling, H. Chen, et al., “Biomimetic Copper Single-Atom Nanozyme System for Self-Enhanced Nanocatalytic tumour Therapy,” Nano Research 15, no. 8 (2022): 7320–7328.

[242] L. Zhang, B. Z. Zhai, Y. J. Wu, and Y. Wang, “Recent Progress in the Development of Nanomaterials Targeting Multiple Cancer Metabolic Pathways: A Review of Mechanistic Approaches for Cancer Treatment,” Drug Delivery 30, no. 1 (2023): 1–18.

[243] H. Maeda, G. Y. Bharate, and J. Daruwalla, “Polymeric Drugs for Efficient tumour-Targeted Drug Delivery Based on EPR-Effect,” European Journal of Pharmaceutics and Biopharmaceutics 71, no. 3 (2009): 409–419.

[244] Y. Ling, D. Nie, Y. Huang, et al., “Antioxidant Cascade Nanoenzyme Antagonize Inflammatory Pain by Modulating MAPK/p-65 Signaling Pathway,” Advanced Science (Weinheim, Germany) 10, no. 12 (2023): e2206934.

[245] C. Yang, W. Liu, S. Chen, et al., “MOF-Immobilized Two-In-One Engineered Enzymes Enhancing Activity of Biocatalytic Cascade for tumour Therapy,” Advanced Healthcare Materials 12, no. 12 (2023): e2203035.

[246] M. Sharifi, R. Kheradmandi, and M. Alizadeh, “Two Birds With One Stone: Triple Negative Breast Cancer Therapy by PtCo Bimetallic Nanozyme Coated With Gemcitabine-Hyaluronic Acid-Polyethylene Glycol,” Cancer Nanotechnology 14, no. 1 (2023): 41.

[247] A. Zhang, A. Gao, C. Zhou, et al., “Confining Prepared Ultrasmall Nanozymes Loading ATO for Lung Cancer Catalytic Therapy/Immunotherapy,” Advanced Materials 35, no. 45 (2023): e2303722.

[248] Z. Xu, J. Jiang, Y. Li, et al., “Shape-Regulated Photothermal-Catalytic tumour Therapy Using Polydopamine@Pt Nanozymes With the Elicitation of an Immune Response,” Small 20, no. 20 (2024): e2309096.

[249] K. Donaldson and C. A. Poland, “Nanotoxicity: Challenging the Myth of Nano-Specific Toxicity,” Current Opinion in Biotechnology 24, no. 4 (2013): 724–734.

[250] L. Yuan, Q. Chen, J. E. Riviere, and Z. Lin, “Pharmacokinetics and tumour Delivery of Nanoparticles,” Journal of Drug Delivery Science and Technology 83 (2023): 104404.

[251] J. Nowak-Jary and B. Machnicka, “In Vivo Biodistribution and Clearance of Magnetic Iron Oxide Nanoparticles for Medical Applications,” International Journal of Nanomedicine 18 (2023): 4067–4100.

[252] Y. Lu, C. Cao, X. Pan, Y. Liu, and D. Cui, “Structure Design Mechanisms and Inflammatory Disease Applications of Nanozymes,” Nanoscale 15, no. 1 (2022): 14–40.

[253] Y. Min, G. G. D. Suminda, Y. Heo, M. Kim, M. Ghosh, and Y. O. Son, “Metal-Based Nanoparticles and Their Relevant Consequences on Cytotoxicity Cascade and Induced Oxidative Stress,” Antioxidants (Basel) 12, no. 3 (2023): 703.

[254] S. Feng, Y. Xuan, H. Jin, et al., “Nanozyme for Precision Treatment of Hepatocellular Carcinoma,” Materials Today Bio 37 (2026): 102840.

[255] R. Yuan, Y. Li, S. Han, et al., “Fe-Curcumin Nanozyme-Mediated Reactive Oxygen Species Scavenging and Anti-Inflammation for Acute Lung Injury,” ACS Central Science 8, no. 1 (2022): 10–21.

[256] J. K. Tee, C. N. Ong, B. H. Bay, H. K. Ho, and D. T. Leong, “Oxidative Stress by Inorganic Nanoparticles,” Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology 8, no. 3 (2016): 414–438.

[257] G. Tarricone, V. Castagnola, V. Mastronardi, et al., “Catalytic Bioswitch of Platinum Nanozymes: Mechanistic Insights of Reactive Oxygen Species Scavenging in the Neurovascular Unit,” Nano Letters 23, no. 10 (2023): 4660–4668.

[258] B. Smolkova, T. MacCulloch, T. F. Rockwood, et al., “Protein Corona Inhibits Endosomal Escape of Functionalized DNA Nanostructures in Living Cells,” ACS Applied Materials & Interfaces 13, no. 39 (2021): 46375–46390.

[259] E. L. Yang, W. Y. Wang, Y. Q. Liu, H. Yi, A. Lei, and Z. J. Sun, “tumour-Targeted Catalytic Immunotherapy,” Advanced Materials 37, no. 5 (2025): e2413210.

[260] S. Wang, Z. Wang, Z. Li, et al., “Amelioration of Systemic Antitumour Immune Responses in Cocktail Therapy by Immunomodulatory Nanozymes,” Science Advances 8, no. 21 (2022): eabn3883.

[261] X. Meng, H. Fan, L. Chen, et al., “Ultrasmall Metal Alloy Nanozymes Mimicking Neutrophil Enzymatic Cascades for tumour Catalytic Therapy,” Nature Communications 15, no. 1 (2024): 1626.

[262] B. Dai, H. Yu, T. Zhang, et al., “Electro-Activated Nanozyme for in Situ tumour Vaccination: Synergistic Multi-Enzyme Catalysis and Electrodynamic Therapy,” Materials Today Bio 35 (2025): 102344.

[263] S. Zhao, J. Hou, L. Deng, et al., “Lactate-Modulating Nanozyme-Mediated Mitochondrial Respiration Block for tumour Immunosuppression Remodeling,” Angewandte Chemie (International Ed. in English) 64, no. 17 (2025): e202422203.

[264] Y. Zhu, Y. Pan, Z. Guo, et al., “Photothermal Enhanced and tumour Microenvironment Responsive Nanozyme for Amplified Cascade Enzyme Catalytic Therapy,” Advanced Healthcare Materials 12, no. 7 (2023): e2202198.

[265] Y. N. Ta, V. T. Nguyen, T. T. Can, et al., “Stimuli-Responsive Nanozyme Reprograms tumour Immunometabolism and Overcomes Therapeutic Resistance in Hepatocellular Carcinoma,” ACS Nano 20, no. 2 (2026): 1870–1884.

[266] Z. Jiang, H. Xiang, and X. Tang, “Smart Inorganic Nanomaterials for tumour Microenvironment Modulation,” Inorganics 13, no. 10 (2025): 337.

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