Engineering polyphenol self-assembly for converged diagnostics and therapy

Polyphenol-based self-assembled nanoplatforms could represent a paradigm-influencing strategy for converged diagnostics and therapy. Their engineering is enabled by catechol/galloyl motifs, which allow programmable supramolecular orchestration and the creation of nanostructures with precise spatiotemporal control. Beyond their role as building blocks, polyphenols contribute a unique pharmacological triad encompassing antioxidant, anti-inflammatory, and autophagy-modulating activities, thereby synergizing with delivered cargos for built-in therapeutic cooperativity. This review first establishes a systematic taxonomy linking polyphenol structural classes to the design and function of self-assembled nanodrug delivery systems (NDDS). It then comprehensively elucidates their advancing applications in precision theranostics, spanning biomarker sensing, multimodal imaging-guided intervention, and targeted therapy for inflammatory diseases, cancers, and infections. Finally, by integrating molecular engineering paradigms with deep mechanistic insights, we could provide a forward-looking framework to navigate persistent translational challenges and support the development of next-generation, closed-loop therapeutic strategies. This work aims to bridge the gap between nanoarchitectonic design and clinical realization in precision medicine.