Mutually Reinforcing Polyphenol and Nanomedicines: Unlocking the Potential of Polyphenol-Based Nanodrugs for Liver...

The liver performs around a thousand essential functions, including metabolism, detoxification, and immune regulation. However, its constant exposure to harmful substances, such as alcohol, drugs, and toxins, makes it prone to injury. Persistent exposure drives liver disease progression, which causes about ∼4% of all deaths annually. Current treatments for liver injury, which combine targeted and supportive care, remain limited by poor drug delivery and efficacy. Anti-inflammatory and antioxidant treatments are essential, yet the pathology is a complex interplay of oxidative stress, inflammation, hepatocyte death, and fibrosis, resisting simple interventions. Polyphenols are multi-target compounds, but their efficacy is hindered by conventional drawbacks. Nanotechnology mimics nanoscale biology to improve pharmacokinetics, enable liver-targeted delivery, and support combination therapies. Notably, polyphenols can act as building units for novel nanodrugs or modify other nanoparticles due to structural features. Thus, polyphenol-based nanodrugs achieve efficient liver enrichment and hold unique potential to tackle multiple therapeutic challenges. Herein, this article analyzes the core pathophysiology of liver injury, elaborates on the biological activities of polyphenols and clinical challenges, and focuses on how to leverage the distinctive chemical properties of polyphenols to construct advanced nanodrugs, and how these nanodrugs can address multiple pathogenic facets of liver injury.