Iron-polyphenol complexes in cancer theranostics: Coordination chemistry, therapeutic mechanisms, and molecular imaging

Background: Iron-polyphenol complexes have emerged as promising theranostic platforms by integrating the biological activity of polyphenols with the redox and coordination properties of iron. Their ability to form discrete molecular complexes and metal-phenolic networks (MPNs) provides tunable control over iron stability, redox activity, cargo delivery, and imaging performance. Since cancer cells exhibit altered iron metabolism and increased dependence on iron availability, these systems offer opportunities for exploiting tumor-specific vulnerabilities through ferroptosis, chemodynamic therapy, and multifunctional molecular imaging. Objectives: This review aims to summarize recent advances in iron-polyphenol systems for cancer theranostics, focusing on the relationship between coordination chemistry, therapeutic mechanisms, and imaging applications. Particular emphasis is placed on discrete Fe-polyphenol complexes, metal-phenolic networks, coordination polymers, and iron-containing hybrid nanoplatforms, including their structural characteristics, anticancer mechanisms, imaging capabilities, biological limitations, and translational challenges. Materials and methods: A structured literature search was conducted using PubMed, Scopus, and Web of Science from database inception to August 2026. Studies related to Fe(II)/Fe(III)-polyphenol coordination systems, including polyphenolic ligands such as catechol, tannic acid, gallic acid, quercetin, and related architectures, were evaluated. Eligible studies included original research investigating coordination chemistry, cancer therapy, molecular imaging, biodistribution, pharmacokinetics, safety, or translational aspects. Non-iron metal-polyphenol systems, iron materials lacking polyphenolic coordination, and unrelated applications were excluded. Results: Iron-polyphenol platforms demonstrate diverse anticancer activities through coordination-controlled mechanisms, including ferroptosis induction, Fe-mediated chemodynamic therapy, photothermal therapy, drug delivery, and immune modulation. The therapeutic and imaging behavior of these systems is strongly influenced by ligand identity, Fe oxidation state, coordination stoichiometry, pH responsiveness, and supramolecular architecture. Iron-polyphenol complexes and MPNs also show potential as gadolinium-free MRI contrast agents, photoacoustic imaging platforms, and immune-cell tracking probes. However, clinical translation remains limited by structural heterogeneity, biological barriers such as protein corona formation and reticuloendothelial system uptake, incomplete biodistribution understanding, long-term iron toxicity concerns, and challenges in scalable manufacturing and quality control. Conclusion: Iron-polyphenol complexes represent a versatile class of theranostic materials that bridge natural product chemistry, redox-regulated cancer therapy, and molecular imaging. Their tunable coordination chemistry enables rational development of multifunctional platforms; however, successful clinical translation requires improved structural standardization, reproducible manufacturing, comprehensive safety evaluation, and quality-controlled production strategies. Continued investigation into coordination-structure-function relationships will be essential for advancing iron-polyphenol systems toward clinically relevant precision cancer theranostics.