Polyphenol-functionalized metal-organic frameworks: A strategic platform for advanced cancer drug delivery and synergistic therapy

Polyphenol-functionalized metal-organic frameworks (MOFs) have emerged as a revolutionary paradigm in cancer therapeutics, combining the structural versatility of MOFs with the bioactive and multifunctional properties of polyphenols. This review comprehensively analyzes recent advancements in the design, synthesis, and biomedical applications of polyphenol-MOF hybrids for targeted drug delivery and synergistic cancer therapy. By leveraging polyphenols such as tannic acid, epigallocatechin gallate (EGCG), gallic acid, and polydopamine, these hybrid systems exhibit enhanced biocompatibility, pH-responsive drug release, and tumor-targeting capabilities. Key innovations include the integration of polyphenol coatings or coordination networks with MOFs (e.g., ZIF-8, MIL-100, UiO-66) to enable stimuli-triggered cargo release, reactive oxygen species (ROS) generation, and multimodal therapeutic effects (chemodynamic, photothermal, and sonodynamic therapy). Case studies highlight the role of polyphenol-MOF hybrids in overcoming limitations of conventional chemotherapy, such as poor drug solubility, off-target toxicity, and multidrug resistance. Furthermore, in vitro and in vivo evaluations demonstrate their efficacy in inducing apoptosis, depleting glutathione (GSH), and enhancing immunotherapy responses. Challenges such as scalability, long-term biosafety, and clinical translation are critically discussed, alongside future directions for engineering next-generation polyphenol-MOF nanoplatforms. This review underscores the transformative potential of polyphenol-MOF hybrids in precision oncology and advocates for their integration into mainstream cancer treatment strategies.