Supramolecular Coordination Platforms for Smart Theranostics: Leveraging the Dynamic Molecular Networks of Metal–Polyphenol Assemblies

Abstract

Metal–polyphenol networks (MPNs), as supramolecular functional materials formed through coordination-driven self-assembly of polyphenol ligands and metal ions (Fe²⁺, Cu²⁺, etc.), have demonstrated broad application prospects in the biomedical field due to their structural designability, excellent biocompatibility, and stimulus-responsive degradation properties. MPNs allow for precise control over coordination kinetics, stability, and functionality through diverse combinations of polyphenols and metal ions. Various assembly methods, including the template method, nanoprecipitation, layer-by-layer self-assembly, and one-pot synthesis, have successfully led to the construction of diverse structures such as films, nanoparticles, hollow capsules, hydrogels, and metal–organic frameworks. By adjusting the metal-to-polyphenol ratio, pH, reaction time, and introducing functional molecules, the size, surface charge, mechanical properties, and dissociation behavior of MPNs can be effectively controlled to meet the demands of various biomedical applications. Leveraging the synergistic interaction between paramagnetic or fluorescent metal ions and polyphenol structures, MPNs are widely used in the design of probes for magnetic resonance imaging, fluorescence imaging, photoacoustic imaging, and multimodal imaging, enabling precise localization and real-time monitoring of pathological sites. MPNs not only serve as highly efficient drug delivery carriers, enabling targeted release in response to the micro acidic or high reactive oxygen species environments of tumors, but also play a critical role in synergistic disease therapy through the enzymatic-like catalytic activity, photothermal conversion capabilities, and radiosensitizing effects of metal ions. In this review, we summarize the advances of MPNs as a highly versatile and functionally integrated supramolecular assembly platform, and discuss their pivotal role in steering biomedical materials away from single-function designs and toward intelligent, unified diagnostic and therapeutic solutions.

Keywords

biomedical imaging / molecular networks / nanoprobe / theranostic / therapy

References

[1] H. Geng, Q. Z. Zhong, J. Li, et al., “Metal Ion-Directed Functional Metal–Phenolic Materials,” Chemical Reviews 122 (2022): 11432–11473.

[2] Z. Lin, H. Liu, J. J. Richardson, et al., “Metal–Phenolic Network Composites: From Fundamentals to Applications,” Chemical Society Reviews 53 (2024): 10800–10826.

[3] Y. Xu, C. Li, X. Ma, et al., “Long Wavelength–Emissive Ru(II) Metallacycle–Based Photosensitizer Assisting in Vivo Bacterial Diagnosis and Antibacterial Treatment,” Proceedings of the National Academy of Sciences of the United States of America 119 (2022): e2209904119.

[4] W. Xu, Z. Lin, C. Cortez-Jugo, et al., “Antimicrobial Phenolic Materials: From Assembly to Function,” Angewandte Chemie International Edition 64 (2025): e202423654.

[5] M. A. Rahim, S. L. Kristufek, S. Pan, et al., “Phenolic Building Blocks for the Assembly of Functional Materials,” Angewandte Chemie International Edition 58 (2018): 1904–1927.

[6] M. K. Mandal, W. Gan, and A. J. Domb, “Phenolate-Based Bioactive Compounds: Design, Delivery and Biomedical Applications,” Coordination Chemistry Reviews 544 (2025): 216941.

[7] Y. Guo, Q. Sun, F. G. Wu, et al., “Polyphenol-Containing Nanoparticles: Synthesis, Properties, and Therapeutic Delivery,” Advanced Materials 33 (2021): 2007356.

[8] W. Abdullah, N. N. A. N. A. Razak, M. A. Dheyab, et al., “Melanin-Driven Green Synthesis and Surface Modification of Metal and Metal-Oxide Nanoparticles for Biomedical Applications,” Advanced Functional Materials 35 (2025): 2503017.

[9] Y. Li, Y. Miao, L. Yang, et al., “Recent Advances in the Development and Antimicrobial Applications of Metal–Phenolic Networks,” Advanced Science 9 (2022): 2202684.

[10] Q. Xing, L. Zhen, X. Zhou, et al., “Cohesion Regulation of Polyphenol Cross-Linked Hydrogel Adhesives: From Intrinsic Cross-Link to Designs of Temporal Responsiveness,” Advanced Functional Materials 35 (2024): 2414294.

[11] A. Ali, R. Javed, S. Farhangi, et al., “Metal Phenolic Networks (MPNs)-Based pH-sensitive Stimulus Responsive Nanosystems for Drug Delivery in Tumor Microenvironment,” Journal of Drug Delivery Science and Technology 84 (2023): 104536.

[12] Y. Xu, C. Li, S. Lu, et al., “Construction of Emissive Ruthenium(II) Metallacycle Over 1000 Nm Wavelength for in Vivo Biomedical Applications,” Nature Communications 13 (2022): 2009.

[13] Z. Lin, N. Goswami, T. Xue, et al., “Engineering Metal Nanoclusters for Targeted Therapeutics: From Targeting Strategies to Therapeutic Applications,” Advanced Functional Materials 31 (2021): 2105662.

[14] Q. Li, Q. Chen, S. Xiao, et al., “A Salidroside-Based Radiosensitizer Regulates the Nrf2/ROS Pathway for X-Ray Activated Synergistic Cancer Precise Therapy,” Advanced Materials 37 (2025): 2413226.

[15] W. Xu, Z. Lin, S. Pan, et al., “Direct Assembly of Metal-Phenolic Network Nanoparticles for Biomedical Applications,” Angewandte Chemie International Edition 62 (2023): e202312925.

[16] Y. Yang, Y. Liu, D. Tu, et al., “Tumor-Microenvironment-Responsive Biodegradable Nanoagents Based on Lanthanide Nucleotide Self-Assemblies Toward Precise Cancer Therapy,” Angewandte Chemie International Edition 134 (2022): e202116983.

[17] R. Yu, H. Chen, J. He, et al., “Engineering Antimicrobial Metal–Phenolic Network Nanoparticles With High Biocompatibility for Wound Healing,” Advanced Materials 36 (2024): 2307680.

[18] Z. Liu, S. Liu, B. Liu, et al., “Tumor Microenvironment-Activatable Metal-Phenolic Nanoformulations for Ultrasound-Boosted Ferroptosis Through Triple Regulatory Pathways,” Advanced Functional Materials 34 (2024): 2407153.

[19] L. Xie, J. Li, G. Wang, et al., “Phototheranostic Metal-Phenolic Networks With Antiexosomal PD-L1 Enhanced Ferroptosis for Synergistic Immunotherapy,” Journal of the American Chemical Society 144 (2022): 787–797.

[20] H. Ejima, J. J. Richardson, and F. Caruso, “Metal-phenolic Networks as a Versatile Platform to Engineer Nanomaterials and Biointerfaces,” Nano Today 12 (2017): 136–148.

[21] Z. Lin, J. J. Richardson, J. Zhou, et al., “Direct Synthesis of Amorphous Coordination Polymers and Metal–Organic Frameworks,” Nature Reviews Chemistry 7 (2023): 273–286.

[22] G. Wang, J. Qin, X. Zhou, et al., “Self-Template Synthesis of Mesoporous Metal Oxide Spheres With Metal-Mediated Inner Architectures and Superior Sensing Performance,” Advanced Functional Materials 28 (2018): 1806144.

[23] J. Guo, B. L. Tardy, A. J. Christofferson, et al., “Modular Assembly of Superstructures From Polyphenol-Functionalized Building Blocks,” Nature Nanotechnology 11 (2016): 1105–1111.

[24] J. Guo, Y. Ping, H. Ejima, et al., “Engineering Multifunctional Capsules Through the Assembly of Metal–Phenolic Networks,” Angewandte Chemie International Edition 53 (2014): 5546–5551.

[25] Y. Ju, C. Cortez-Jugo, J. Chen, et al., “Engineering of Nebulized Metal–Phenolic Capsules for Controlled Pulmonary Deposition,” Advanced Science 7 (2020): 1902650.

[26] S. K. Bhangu, P. Charchar, B. B. Noble, et al., “Origins of Structural Elasticity in Metal–Phenolic Networks Probed by Super-Resolution Microscopy and Multiscale Simulations,” ACS Nano 16 (2021): 98–110.

[27] Y. Han, Z. Lin, J. Zhou, et al., “Polyphenol-Mediated Assembly of Proteins for Engineering Functional Materials,” Angewandte Chemie International Edition 59 (2020): 15618–15625.

[28] Z. Lin, J. Zhou, C. Cortez-Jugo, et al., “Ordered Mesoporous Metal–Phenolic Network Particles,” Journal of the American Chemical Society 142 (2019): 335–341.

[29] G. Yun, Q. A. Besford, S. T. Johnston, et al., “Self-Assembly of Nano- to Macroscopic Metal–Phenolic Materials,” Chemistry of Materials 30 (2018): 5750–5758.

[30] X. Tan, R. Sheng, W. Li, et al., “Mannose-Glycated Metal-Phenolic Microcapsules Orchestrate Phenotype Switch of Macrophages for Boosting Tumor Immunotherapy,” Advanced Science 12 (2025): 2415565.

[31] P. Liu, X. Shi, S. Zhong, et al., “Metal-phenolic Networks for Cancer Theranostics,” Biomaterials Science 9 (2021): 2825–2849.

[32] J. Li, B. Ding, P. Zheng, et al., “Construction of Diverse Calcium-Based Nanomaterials Through a Microemulsion Method for Pyroptosis-Initiated Antitumor Immunotherapy,” Advanced Materials 38 (2026): e16225.

[33] D. Wu, B. Zhou, S. Wang, et al., “Pickering Emulsion Stabilized by Metal-Phenolic Architectures: A Straightforward in Situ Assembly Strategy,” Journal of Agricultural and Food Chemistry 69 (2021): 11709–11719.

[34] Q. A. Besford, Y. Ju, T. Y. Wang, et al., “Self-Assembled Metal–Phenolic Networks on Emulsions as Low-Fouling and pH-Responsive Particles,” Small 14 (2018): 1802342.

[35] Z. Tang, Z. Huang, Y. Huang, et al., “Nanomedicine's Shining Armor: Understanding and Leveraging the Metal-phenolic Networks,” Journal of Nanobiotechnology 23 (2025): 158.

[36] Y. Liang, Z. Li, Y. Huang, et al., “Dual-Dynamic-Bond Cross-Linked Antibacterial Adhesive Hydrogel Sealants With on-Demand Removability for Post-Wound-Closure and Infected Wound Healing,” ACS Nano 15 (2021): 7078–7093.

[37] Q. Yang, R. Chen, M. Li, et al., “High Antimicrobial Electrotherapy and Wound Monitoring Hydrogel With Bimetal Phenolic Networks for Smart Healthcare,” Advanced Functional Materials 35 (2025): 2413080.

[38] H. Zhang, J. Zhang, B. Liu, et al., “Natural Phenolic-Metal Framework Strengthened Mesona Chinensis Polysaccharides Microgels for Improved Viability of Probiotics to Alleviate the Liver Injury and Gut Microbiota Dysbiosis,” Advanced Functional Materials 34 (2024): 2401064.

[39] G. Fan, P. Wasuwanich, M. R. Rodriguez-Otero, et al., “Protection of Anaerobic Microbes From Processing Stressors Using Metal–Phenolic Networks,” Journal of the American Chemical Society 144 (2021): 2438–2443.

[40] Z. Lin, J. Zhou, Y. Qu, et al., “Luminescent Metal-Phenolic Networks for Multicolor Particle Labeling,” Angewandte Chemie International Edition 60 (2021): 24968–24975.

[41] J. H. Park, K. Kim, J. Lee, et al., “A Cytoprotective and Degradable Metal–Polyphenol Nanoshell for Single-Cell Encapsulation,” Angewandte Chemie International Edition 53 (2014): 12420–12425.

[42] X. Li, H. Liu, Z. Lin, et al., “Cytoprotective Metal–Phenolic Network Sporulation to Modulate Microalgal Mobility and Division,” Advanced Science 11 (2024): e2308026.

[43] X. He, G. Gong, M. Chen, et al., “Metal-Phenolic Nanocloaks on Cancer Cells Potentiate STING Pathway Activation for Synergistic Cancer Immunotherapy,” Angewandte Chemie International Edition 63 (2024): e202314501.

[44] J. Yan, G. Wang, L. Xie, et al., “Engineering Radiosensitizer-Based Metal-Phenolic Networks Potentiate STING Pathway Activation for Advanced Radiotherapy,” Advanced Materials 34 (2022): 2105783.

[45] Z. Guo, X. Gao, J. Lu, et al., “Apoptosis and Paraptosis Induced by Disulfiram-Loaded Ca2+/Cu2+ Dual-Ions Nano Trap for Breast Cancer Treatment,” ACS Nano 18 (2024): 6975–6989.

[46] L. Li, Z. Yang, W. Fan, et al., “In Situ Polymerized Hollow Mesoporous Organosilica Biocatalysis Nanoreactor for Enhancing ROS-Mediated Anticancer Therapy,” Advanced Functional Materials 30 (2020): 1907716.

[47] Q. He, S. Yuan, H. Tang, et al., “Safeguarding Osteointegration in Diabetic Patients: A Potent “Chain Armor” Coating for Scavenging ROS and Macrophage Reprogramming in a Microenvironment-Responsive Manner,” Advanced Functional Materials 31 (2021): 2101611.

[48] S. Pan, Y. Lan, Y. Yang, et al., “Metal-Polyphenol Network Coated Bilirubin Nanoparticles for the Alleviation of Periodontitis via Mild Photothermal Therapy and Immunomodulatory Therapy,” ACS Nano 19 (2025): 23919–23944.

[49] X. Sun, X. Liang, Y. Wang, et al., “A Tumor Microenvironment-activatable Nanoplatform With Phycocyanin-assisted in-situ Nanoagent Generation for Synergistic Treatment of Colorectal Cancer,” Biomaterials 301 (2023): 122263.

[50] L. Jiang, Y. Zeng, H. Li, et al., “Peptide-Based Coacervate Protocells With Cytoprotective Metal–Phenolic Network Membranes,” Journal of the American Chemical Society 145 (2023): 24108–24115.

[51] X. Zhang, Z. Yuan, J. Wu, et al., “An Orally-Administered Nanotherapeutics With Carbon Monoxide Supplying for Inflammatory Bowel Disease Therapy by Scavenging Oxidative Stress and Restoring Gut Immune Homeostasis,” ACS Nano 17 (2023): 21116–21133.

[52] H. He, Q. Qin, and F. Xu, “Oral Polyphenol-Armored Nanomedicine for Targeted Modulation of Gut Microbiota–Brain Interactions in Colitis,” Science Advances 9 (2023): eadf3887.

[53] O. Mazaheri, Z. Lin, W. Xu, et al., “Assembly of Silicate–Phenolic Network Coatings With Tunable Properties for Controlled Release of Small Molecules,” Advanced Materials 36 (2024): 2413349.

[54] B. Liu, F. Hu, J. Zhang, et al., “A Biomimetic Coordination Nanoplatform for Controlled Encapsulation and Delivery of Drug–Gene Combinations,” Angewandte Chemie International Edition 58 (2019): 8804–8808.

[55] X. Song, Z. Zheng, S. Ouyang, et al., “Biomimetic Epigallocatechin Gallate–Cerium Assemblies for the Treatment of Rheumatoid Arthritis,” ACS Applied Materials & Interfaces 15 (2023): 33239–33249.

[56] Z. Wang, Y. Guo, G. Li, et al., “Biomimetic Metal-Phenolic Network-Coated Elastin-Like Polypeptide Micelles as an Immunogenic Cell Death Inducer for Orthotopic Glioma Sonodynamic-Chemodynamic-Immune Therapy,” Nano Today 64 (2025): 102810.

[57] J. Li, J. Song, Z. Deng, et al., “Robust Reactive Oxygen Species Modulator Hitchhiking Yeast Microcapsules for Colitis Alleviation by Trilogically Intestinal Microenvironment Renovation,” Bioactive Materials 36 (2024): 203–220.

[58] L. Wan, S. Li, J. Du, et al., “Review of Metal–Polyphenol Self-Assembled Nanoparticles: Synthesis, Properties, and Biological Applications in Inflammatory Diseases,” ACS Biomaterials Science & Engineering 11 (2025): 2502–2527.

[59] H. Luo, J. Xie, X. Su, et al., “Tannic Acid-Based Metal-Phenolic Networks as a Versatile Platform to Mediate Cell Therapy,” Science China Materials 67 (2024): 3833–3848.

[60] F. Wu, C. Song, H. Yin, et al., “Metal Phenolic Networks-Driven Bufalin Homodimeric Prodrug Nano-Coassemblies for Ferroptosis-Augmented Tumor Therapy,” Journal of Controlled Release 383 (2025): 113814.

[61] R. Xing, Q. Zou, C. Yuan, et al., “Self-Assembling Endogenous Biliverdin as a Versatile Near-Infrared Photothermal Nanoagent for Cancer Theranostics,” Advanced Materials 31 (2019): 1900822.

[62] X. He, H. Zhu, J. Shang, et al., “Intratumoral Synthesis of Transformable Metal-Phenolic Nanoaggregates With Enhanced Tumor Penetration and Retention for Photothermal Immunotherapy,” Theranostics 12 (2022): 6258–6272.

[63] J. Su, F. Chen, V. L. Cryns, et al., “Catechol Polymers for pH-Responsive, Targeted Drug Delivery to Cancer Cells,” Journal of the American Chemical Society 133 (2011): 11850–11853.

[64] H. Ejima, J. Richardson, and K. Liang, “One-Step Assembly of Coordination Complexes for Versatile Film and Particle Engineering,” Science 341 (2013): 154–157.

[65] H. Zeng, D. Li, Q. He, et al., “A Microenvironment Responsive Nanoparticle Regulating Osteoclast Fate to Promote Bone Repair in Osteomyelitis,” Materials Today Bio 32 (2025): 101777.

[66] S. Liang, H. Ma, Y. Liu, et al., “Nano-Immunomodulator Amplifies STING Activation in Tumor-Associated Macrophages for Cancer Immunotherapy,” Journal of Controlled Release 383 (2025): 113846.

[67] Y. Xiong, Z. Yong, S. Li, et al., “Self-Reliant Nanomedicine With Long-Lasting Glutathione Depletion Ability Disrupts Adaptive Redox Homeostasis and Suppresses Cancer Stem Cells,” Advanced Functional Materials 34 (2024): 2310158.

[68] Y. Xiong, Z. Yong, C. Xu, et al., “Hyperbaric Oxygen Activates Enzyme-Driven Cascade Reactions for Cooperative Cancer Therapy and Cancer Stem Cells Elimination,” Advanced Science 10 (2023): 2301278.

[69] T. Ding, Z. Wang, D. Xia, et al., “Long-Lasting Reactive Oxygen Species Generation by Porous Redox Mediator-Potentiated Nanoreactor for Effective Tumor Therapy,” Advanced Functional Materials 31 (2021): 2008573.

[70] F. Liu, Y. Chen, Y. Huang, et al., “Synergistic Wall Digestion and Cuproptosis Against Fungal Infections Using Lywallzyme-Induced Self-Assembly of Metal-Phenolic Nanoflowers,” Nature Communications 15 (2024): 9004.

[71] X. Chen, W. Wu, W. Zhu, et al., “Regulation of Bone Remodeling by Metal–Phenolic Networks for the Treatment of Systemic Osteoporosis,” ACS Applied Materials & Interfaces 17 (2025): 5995–6008.

[72] G. Wang, J. Yan, H. Tian, et al., “Dual-Epigenetically Relieving the MYC-Correlated Immunosuppression via an Advanced Nano-Radiosensitizer Potentiates Cancer Immuno-Radiotherapy,” Advanced Materials 36 (2024): 2312588.

[73] F. Shao, J. Han, Z. Tian, et al., “Synergistic ROS Generation and Directional Overloading of Endogenous Calcium Induce Mitochondrial Dysfunction in Living Cells,” Biomaterials 301 (2023): 122284.

[74] Y. Xu, Y. Luo, Z. Weng, et al., “Microenvironment-Responsive Metal-Phenolic Nanozyme Release Platform With Antibacterial, ROS Scavenging, and Osteogenesis for Periodontitis,” ACS Nano 17 (2023): 18732–18746.

[75] J. Hu, X. Wang, Q. Sun, et al., “A Polysaccharide Metal Phenolic Network Nanocomposite for Theranostic Applications in Inflammatory Bowel Disease,” Advanced Functional Materials 35 (2024): 2416918.

[76] Y. Li, R. Fu, Z. Duan, et al., “Construction of Multifunctional Hydrogel Based on the Tannic Acid-metal Coating Decorated MoS2 Dual Nanozyme for Bacteria-Infected Wound Healing,” Bioactive Materials 9 (2022): 461–474.

[77] X. Liu, B. Chen, J. Chen, et al., “A Cardiac-Targeted Nanozyme Interrupts the Inflammation-Free Radical Cycle in Myocardial Infarction,” Advanced Materials 36 (2023): 2308477.

[78] Z. Wei, L. Wang, C. Tang, et al., “Metal-Phenolic Networks Nanoplatform to Mimic Antioxidant Defense System for Broad-Spectrum Radical Eliminating and Endotoxemia Treatment,” Advanced Functional Materials 30 (2020): 2002234.

[79] J. Gu, P. Zhang, H. Li, et al., “Cerium–Luteolin Nanocomplexes in Managing Inflammation-Related Diseases by Antioxidant and Immunoregulation,” ACS Nano 18 (2024): 6229–6242.

[80] X. Huang, F. Zhang, Y. Yang, et al., “Curcumin-Copper Complex Nanoparticles as Antioxidant Nanozymes for Acute Kidney Injury Alleviation,” Materials Today Bio 32 (2025): 101794.

[81] W. He, M. Liu, T. Zhang, et al., “Tannic Acid–Iron Complex-Based Nanozyme Ameliorates Parkinson's Disease via Relieving Oxidative Stress and Neuroinflammation,” ACS Nano 19 (2025): 33212–33229.

[82] 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 (2021): 10–21.

[83] C. Pucci, C. Martinelli, D. De Pasquale, et al., “Tannic Acid–Iron Complex-Based Nanoparticles as a Novel Tool Against Oxidative Stress,” ACS Applied Materials & Interfaces 14 (2022): 15927–15941.

[84] M. Ou, K. Zhang, G. Liao, et al., “Polyphenol-Regulated Bimetallic Artificial Metalloproteinases With Broad-Spectrum RONS Scavenging Activities for Diabetic Wound Repair,” Advanced Functional Materials 35 (2025): 2501438.

[85] K. Liu, S. Chen, X. Geng, et al., “Multifunctional Selenium-Based Metal Polyphenol Nanoparticles Impede the Pathological Cross-Talk Between Reactive Oxygen Species and Inflammation in Sepsis,” ACS Materials Letters 6 (2024): 2434–2445.

[86] J. Li, T. Wu, W. Wang, et al., “Hybrid Nanoparticle–Mediated Simultaneous ROS Scavenging and STING Activation Improve the Antitumor Immunity of in Situ Vaccines,” Science Advances 10 (2024): eadn3002.

[87] Q. Chen, Q. Qian, H. Xu, et al., “Mitochondrial-Targeted Metal-Phenolic Nanoparticles to Attenuate Intervertebral Disc Degeneration: Alleviating Oxidative Stress and Mitochondrial Dysfunction,” ACS Nano 18 (2024): 8885–8905.

[88] S. Mao, Y. Ren, W. Tan, et al., “Orally ROS/pH Dual-Responsive and Targeted Fucoxanthin Microspheres for the Alleviation of Colon Inflammation,” Small 21 (2025): e03476.

[89] H. Xu, Z. Zhao, P. She, et al., “Salvaging Myocardial Infarction With Nanoenzyme-Loaded Hydrogels: Targeted Scavenging of Mitochondrial Reactive Oxygen Species,” Journal of Controlled Release 375 (2024): 788–801.

[90] T. Zheng, J. Sheng, Z. Wang, et al., “Injured Myocardium-Targeted Theranostic Nanoplatform for Multi-Dimensional Immune-Inflammation Regulation in Acute Myocardial Infarction,” Advanced Science 12 (2025): 2414740.

[91] J. Chen, C. Cortez-Jugo, C. J. Kim, et al., “Metal–Phenolic-Mediated Assembly of Functional Small Molecules Into Nanoparticles: Assembly and Bioapplications,” Angewandte Chemie International Edition 63 (2024): e202319583.

[92] W. Zhang, Q. A. Besford, A. J. Christofferson, et al., “Cobalt-Directed Assembly of Antibodies Onto Metal–Phenolic Networks for Enhanced Particle Targeting,” Nano Letters 20 (2020): 2660–2666.

[93] H. Zhou, Q. Qian, Q. Chen, et al., “Enhanced Mitochondrial Targeting and Inhibition of Pyroptosis With Multifunctional Metallopolyphenol Nanoparticles in Intervertebral Disc Degeneration,” Small 20 (2023): 2308167.

[94] W. Feng, W. Shi, S. Liu, et al., “Fe(III)-Shikonin Supramolecular Nanomedicine for Combined Therapy of Tumor via Ferroptosis and Necroptosis,” Advanced Healthcare Materials 11 (2021): 2101926.

[95] H. Mao, Y. Wen, Y. Yu, et al., “Ignored Role of Polyphenol in Boosting Reactive Oxygen Species Generation for Polyphenol/Chemodynamic Combination Therapy,” Materials Today Bio 16 (2022): 100436.

[96] Z. Zhang, D. Cheng, D. Liu, et al., “Bioengineered Versatile Heterojunctions as Stress Busters Targeting Matrix Degradation and Ferroptosis for Osteoarthritis Therapy,” Advanced Functional Materials 35 (2025): 2419400.

[97] H. Gong, L. Yang, Y. Li, et al., “Metal-Polyphenol Nanocomposite Hybrid Hydrogel: A Multifunctional Platform for Treating Diabetic Foot Ulcers Through Metabolic Microenvironment Reprogramming,” Biomaterials 322 (2025): 123414.

[98] T. Yuan, W. Liu, T. Wang, et al., “Natural Polyphenol Delivered Methylprednisolone Achieve Targeted Enrichment for Acute Spinal Cord Injury Therapy,” Small 20 (2024): 2404815.

[99] R. Jiang, J. Rao, H. Su, et al., “Degradable Metal-Small Molecule Drug Coordination Nanomedicines for DNA Damage-Augmented Cancer Chemodynamic Therapy,” Small 21 (2025): 2501721.

[100] J. Li, G. Gong, Y. Zhang, et al., “Polyphenol-Nanoengineered Monocyte Biohybrids for Targeted Cardiac Repair and Immunomodulation,” Advanced Healthcare Materials 14 (2024): 2403595.

[101] Q. Shen, L. Wang, X. Ruan, et al., “Stimuli-Responsive Organic Near-Infrared Photoacoustic Probes,” Advanced Functional Materials 33 (2023): 2300023.

[102] H. He, Q. Qin, F. Xu, et al., “Oral Polyphenol-Armored Nanomedicine for Targeted Modulation of Gut Microbiota–Brain Interactions in Colitis,” Science Advances 9 (2023): eadf3887.

[103] Y. Gao, S. C. Yang, M. H. Zhu, et al., “Metal Phenolic Network-Integrated Multistage Nanosystem for Enhanced Drug Delivery to Solid Tumors,” Small 17 (2021): 2100789.

[104] H. Luo, F. Wu, X. Wang, S. Lin, et al., “Encoding Bacterial Colonization and Therapeutic Modality by Wrapping With an Adhesive Drug-Loadable Nanocoating,” Materials Today 62 (2023): 98–110.

[105] J. Pan, G. Gong, Q. Wang, et al., “A Single-Cell Nanocoating of Probiotics for Enhanced Amelioration of Antibiotic-Associated Diarrhea,” Nature Communications 13 (2022): 2117.

[106] J. Wang, W. Sang, Z. Yang, et al., “Polyphenol-Based Nanoplatform for MRI/PET Dual-Modality Imaging Guided Effective Combination Chemotherapy,” Journal of Materials Chemistry B 7 (2019): 5688–5694.

[107] J. Qin, G. Liang, B. Feng, et al., “Facile Synthesis of Metal-Polyphenol-Formaldehyde Coordination Polymer Colloidal Nanoparticles With Sub-50 Nm for T1-weighted Magnetic Resonance Imaging,” Chinese Chemical Letters 32 (2021): 842–848.

[108] W. Yang, C. Deng, X. Shi, et al., “Structural and Molecular Fusion MRI Nanoprobe for Differential Diagnosis of Malignant Tumors and Follow-Up Chemodynamic Therapy,” ACS Nano 17 (2023): 4009–4022.

[109] Z. Zhang, W. Sang, L. Xie, et al., “Polyphenol-Based Nanomedicine Evokes Immune Activation for Combination Cancer Treatment,” Angewandte Chemie International Edition 60 (2020): 1967–1975.

[110] H. Tian, W. Li, and G. Wang, “Metal-Phenolic Nanomaterial With Organelle-Level Precision Primes Antitumor Immunity via mtDNA-Dependent cGAS-STING Activation,” Angewandte Chemie International Edition 63 (2024): e202411498.

[111] Y. Wang, Z. Wang, C. Xu, et al., “A Disassembling Strategy Overcomes the EPR Effect and Renal Clearance Dilemma of the Multifunctional Theranostic Nanoparticles for Cancer Therapy,” Biomaterials 197 (2019): 284–293.

[112] G. G. Yang, D. J. Zhou, Z. Y. Pan, et al., “Multifunctional Low-Temperature Photothermal Nanodrug With in Vivo Clearance, ROS-Scavenging and Anti-Inflammatory Abilities,” Biomaterials 216 (2019): 119280.

[113] C. Zhu, Y. Wang, Z. Li, et al., “Metallopolysaccharide-Based Smart Nanotheranostic for Imaging Guided Precise Phototherapy and Sequential Enzyme-Activated Ferroptosis,” Biomacromolecules 23 (2022): 2007–2018.

[114] J. Meng, L. Wang, Q. Wang, et al., “Construction of Artificial Controllable Aggregation Trojan HorseLike Nanoplatform for Enhanced NIR-II Photothermal Therapy,” ACS Applied Materials & Interfaces 15 (2023): 4903–4910.

[115] S. Shen, D. Jiang, L. Cheng, et al., “Renal-Clearable Ultrasmall Coordination Polymer Nanodots for Chelator-Free 64Cu Labeling and Imaging-Guided Enhanced Radiotherapy of Cancer,” ACS Nano 11 (2017): 9103–9111.

[116] Y. Dai, Z. Yang, S. Cheng, et al., “Toxic Reactive Oxygen Species Enhanced Synergistic Combination Therapy by Self-Assembled Metal-Phenolic Network Nanoparticles,” Advanced Materials 30 (2018): 1704877.

[117] Q. Wang, Y. Xu, R. Xue, et al., “All-in-One Theranostic Platform Based on Hollow Microcapsules for Intragastric-Targeting Antiulcer Drug Delivery, CT Imaging, and Synergistically Healing Gastric Ulcer,” Small 18 (2022): 2104660.

[118] Z. Liu, P. Ma, and J. Lin, “Harnessing Engineered Metal-Phenolic Networks as Theranostic Nanomedicines for Cancer Treatments,” Coordination Chemistry Reviews 548 (2026): 217230.

[119] J. Wang, Q. Tian, Y. Liu, et al., “Targeting Metalloptosis in Tumor Therapy: From Molecular Mechanisms to Application of Metal Nanoparticles,” Molecular Cancer 24 (2025): 260.

[120] S. Wang, R. Ma, Z. Mei, et al., “Metalloptosis: Metal Ions-Induced Programmed Cell Death Based on Nanomaterials for Cancer Therapy,” Medical Materials 1 (2024): 6–26.

[121] S. Dixon, K. Lemberg, M. Lamprecht, et al., “Ferroptosis: An Iron-Dependent Form of Nonapoptotic Cell Death,” Cell 149 (2012): 1060–1072.

[122] J. Yan, W. Li, H. Tian, et al., “Metal-Phenolic Nanomedicines Regulate T-Cell Antitumor Function for Sono-Metabolic Cancer Therapy,” ACS Nano 17 (2023): 14667–14677.

[123] W. Li, H. Tian, Z. Yan, et al., “Magnesium-Phenolic Nanoeditor Refining Gliomatous T Cells for Metalloimmunotherapy,” ACS Nano 19 (2025): 1222–1237.

[124] G. Zhu, Y. Xie, J. Wang, et al., “Multifunctional Copper-Phenolic Nanopills Achieve Comprehensive Polyamines Depletion to Provoke Enhanced Pyroptosis and Cuproptosis for Cancer Immunotherapy,” Advanced Materials 36 (2024): 2409066.

[125] W. Sun, H. Wang, Y. Qi, et al., “Metal-Phenolic Vehicles Potentiate Cycle-Cascade Activation of Pyroptosis and cGAS-STING Pathway for Tumor Immunotherapy,” ACS Nano 18 (2024): 23727–23740.

[126] N. Wang, X. Zhang, Z. Gao, et al., “Personalized Vaccination of Tumor-Derived Antigens and STING Agonists for Specific Cancer Immunotherapy,” Advanced Materials 38 (2026): e20325.

[127] W. Sang, Z. Zhang, G. Wang, et al., “A Triple-Kill Strategy for Tumor Eradication Reinforced by Metal-Phenolic Network Nanopumps,” Advanced Functional Materials 32 (2022): 2113168.

[128] S. Fang, Y. Song, M. Sun, et al., “Continuous Spatiotemporal Therapy of a Full-API Nanodrug via Multi-Step Tandem Endogenous Biosynthesis,” Nature Communications 14 (2023): 1660.

[129] M. Meng, J. Wu, Y. Feng, et al., “A Comprehensive Strategy Based on High Clinical Translational Nanosystem for Programmable Immunotherapy of Triple Negative Breast Cancer,” Advanced Materials 36 (2024): 2314309.

[130] J. Zhang, J. Li, X. Jiang, et al., “Mitochondria Rewiring by Polyphenol-Copper Nanodots to Truncate Mitochondrial-Endoplasmic Reticulum Crosstalk for Acute Kidney Injury Therapy,” Advanced Materials 38 (2025): e08379.

[131] Y. Kong, X. Chen, F. Liu, et al., “Ultrasmall Polyphenol-NAD+ Nanoparticle-Mediated Renal Delivery for Mitochondrial Repair and Anti-Inflammatory Treatment of AKI-to-CKD Progression,” Advanced Materials 36 (2024): 2310731.

[132] J. Hu, X. Wang, Q. Sun, et al., “A Polysaccharide Metal Phenolic Network Nanocomposite for Theranostic Applications in Inflammatory Bowel Disease,” Advanced Functional Materials 35 (2025): 2416918.

[133] Y. Huang, Q. Gao, C. Li, et al., “Facile Synthesis of Zn2+-Based Hybrid Nanoparticles as a New Paradigm for the Treatment of Internal Bacterial Infections,” Advanced Functional Materials 32 (2022): 2109011.

[134] A. Frei, A. Verderosa, A. Elliott, et al., “Metals to Combat Antimicrobial Resistance,” Nature Reviews Chemistry 7 (2023): 202–224.

[135] B. Kaczmarek, “Tannic Acid With Antiviral and Antibacterial Activity as a Promising Component of Biomaterials-A Minireview,” Materials 13 (2020): 3224.

[136] M. Nikoo, J. Regenstein, and H. Gavlighi, “Antioxidant and Antimicrobial Activities of (-)-Epigallocatechin-3-gallate (EGCG) and Its Potential to Preserve the Quality and Safety of Foods,” Comprehensive Reviews in Food Science and Food Safety 17 (2018): 732–753.

[137] R. Yu, H. Chen, and J. He, “Engineering Antimicrobial Metal–Phenolic Network Nanoparticles With High Biocompatibility for Wound Healing,” Advanced Materials 36 (2024): 2307680.

[138] V. Choi, J. L. Rohn, P. Stoodley, et al., “Drug Delivery Strategies for Antibiofilm Therapy,” Nature Reviews Microbiology 21 (2023): 555–572.

[139] Y. Ni, Y. Huang, Y. Chen, et al., “An Inhalable Gallium-Polyphenol Nanoparticle Blocks Bacterial Electron Transport Chain and Signal Transduction for Anti-Biofilm Therapy,” Bioactive Materials 57 (2026): 1–15.

[140] J. Li, Z. Deng, X. Liang, et al., “A Smart ROS-Responsive Hydrogel for On-Demand Antibacterial and Platelet-Rich Plasma (PRP) Activation in Diabetic Wound Healing,” Journal of Controlled Release 388 (2025): 114392.

Rights & permissions

2026 The Author(s). Aggregate published by SCUT, AIEI, and John Wiley & Sons Australia, Ltd.