Emerging Self-Assembled Nanoparticles Constructed from Natural Polyphenols for Intestinal Diseases

Intestinal diseases like inflammatory bowel disease (IBD) and colorectal cancer originate from inflammation and disruption of mucosal barriers. Polyphenols can mitigate intestinal inflammation through antioxidant, anti-inflammatory, and microbiome modulation effects. However, the poor solubility and stability of polyphenols restrict therapeutic delivery. Self-assembly provides a nanoscale platform to overcome these limitations. Polyphenol-based nanoparticles (PNPs) are formed via coordination of polyphenols with metals like iron, copper, and zinc based on the catechol/galloyl groups. Templeted assembly with amphiphilic block copolymers can also direct polyphenol self-assembly into nanostructures. PNPs prepared by these mild, aqueous methods exhibit enhanced stability, pH-responsive disassembly, high cargo-loading capacity, and targeted accumulation in inflamed intestinal tissues. PNPs can load with hydrophobic polyphenols, drugs, genes, proteins, or probiotics and demonstrate therapeutic potential in preclinical IBD, colorectal cancer, and microbiome disorder models. Ongoing challenges include augmenting prebiotic effects, multidrug encapsulation, and engineering PNPs as biotherapeutics. Future directions involve tailored polyphenol–polymer covalent assemblies and investigating PNPs interactions with enterocytes, immune cells, and microbiota. Overall, PNPs prepared by facile self-assembly combine the bioactivities of polyphenols with advanced delivery functionality, presenting new opportunities for combination and microbiota-based therapies for complex intestinal diseases.