Epigenetic Targets of Polyphenolic Nanoparticles in Cancer: Current Insights

Epigenetic dysregulation such as aberrant DNA methylation, histone modifications, and non-coding RNA imbalance is now recognized as a central driver of tumour initiation, progression, and therapeutic resistance. Polyphenols, a diverse class of plant-derived metabolites, have demonstrated significant epigenetic remodelling activity; however, their therapeutic potential is hampered by poor solubility, rapid metabolism, and limited bioavailability. Nanoparticle-based delivery systems have emerged as a promising strategy to overcome these barriers, enabling targeted accumulation of polyphenols within tumour tissues and enhancing their mechanistic impact on epigenetic pathways. This review synthesizes recent advances in polyphenol-loaded nanocarriers such as liposomes, polymeric nanoparticles, dendrimers, and solid lipid nanoparticles highlighting their ability to modulate DNMTs, HDACs, HATs, PRC2 components, and tumour-associated microRNAs and lncRNAs. We also compare in vitro and in vivo findings, discuss pharmacokinetic improvements, and identify key challenges including nanoparticle stability, immune interactions, protein corona formation, and off-target epigenetic effects. Overall, nano-enabled polyphenolic platforms represent a promising frontier for selective epigenetic cancer therapy, yet require rigorous evaluation and translational validation to move toward clinical application.