Bioactivity and Mechanistic Insights of Flavonoids for Advanced Cancer Nanotherapeutics

Flavonoids represent one of the most diverse and pharmacologically important classes of phytometabolites, recognized for their versatile therapeutic roles in cancer prevention and treatment. They are grouped into various subclasses including flavones, flavanones, flavanonols, flavanols, isoflavones, anthocyanidins, and chalcones according to their structural diversity. They exhibit anticancer effects by modulating multiple signaling pathways, regulation of inflammatory mediators, inhibition of angiogenesis, and oxidative stress-mediated apoptosis. However, despite their promising pharmacodynamics, the clinical translation of flavonoids remains limited due to poor solubility, limited cellular uptake, poor bioavailability, and rapid clearance. Nanotechnology has emerged as a transformative strategy to overcome these limitations. Certain nanocarrier-based delivery systems including liposomes, metallic nanoparticles, dendrimers, polymeric nanoparticles, hydrogels, and protein-based nanocarriers have been conjugated with flavonoids to enhance their bioavailability and promote selective cytotoxicity. However, evaluation of safety profiles and clinical translation of flavonoids and their nanoconjugates pose major limitations that need to be addressed. This chapter systematically outlines classification of flavonoids, mechanistic anticancer pathways, and recent advances in nanoparticle-mediated flavonoid delivery for cancer treatment.