One-step green assembly of natural polyphenol-based nobiletin nanoparticles for ulcerative colitis therapy

Function-inspired design of natural building blocks enables engineering nanostructured particles for tailored applications. Here, a facile coordination-driven assembly of natural polyphenols was proposed for incorporating hydrophobic citrus-derived nobiletin (NOB) into the nanoparticles (NPs) via a one-pot method in aqueous solutions. The obtained NPs provide high NOB encapsulation efficiency with small, but uniform size (≈250 nm). Moreover, they possessed prolonged colloidal stability and excellent biocompatibility and achieved robust therapeutic efficacy in alleviating ulcerative colitis (UC), in comparison with free NOB. Mechanistically, the desirable NPs maximized the inherent anti-inflammatory and antioxidant activities of natural building blocks, enabling effective attenuation of intestinal inflammation and oxidative stress, thus contributing to the restoration of the intestinal mucosal barrier and immune homeostasis. Overall, this work proposes a promising self-assembly strategy to improve the bioavailability and therapeutic potential of natural flavonoids for the treatment of UC, and ultimately offering potential benefits for patients suffering from it. A one-step green assembly strategy for the efficient incorporation of NOB into flexible metal-phenolic networks (MPNs) offers a versatile nanoplatform for the effective alleviation in DSS-induced ulcerative colitis. • Nobiletin crystallization was regulated by metal-phenolic networks mediated assembly strategy. • The colloidal NTAl NPs alleviate colitis with protective and therapeutic effects. • NTAl NPs effectively modulate inflammation and oxidative stress, promoting intestinal immune homeostasis.