Metal-phenolic networks: a favorable combination for disease treatment

Metal ions and polyphenols possess special pharmacological activities and are widely researched for various disease treatments. When they undergo a favorable combination, metal-phenolic networks (MPNs) are formed through the coordination-driven self-assembly between polyphenols and metal ions. MPNs are widely used as multifunctional nanoplatforms, combining the pharmacological properties of metal ions with the biological functions of polyphenols, as well as possessing targeted delivery and microenvironment-responsiveness. This review provides a systematic summary of the physicochemical properties and pharmacological mechanisms of polyphenolic compounds (e.g., EGCG, TA) and metal ions (Fe 3+ , Cu 2+ , Zn 2+ , etc.), and elaborates on the fabrication strategies of MPNs and their applications in the treatment of tumors, infections, inflammation, degenerative disorders, and other diseases. The synergistic mechanisms of MPNs for disease treatment are emphasized, including ferroptosis, cuproptosis, and immunomodulation. We also address the challenges and improvement strategies of MPNs for their clinical translation. This work provides a foundation for the rational design and expansion of biomedical applications of MPNs.