Abstract

The worldwide incidence and prevalence of inflammatory bowel disease (IBD) is increasing at an alarming rate, requiring the development of safe and effective therapeutic interventions. The use of oxidative stress and accelerated resolution of reactive oxygen species (ROS) has emerged as a potential new strategy for the management of inflammatory diseases. In this study, we described the development of a novel class of foodborne NPs-alginate-hyaluronic acid-anthocyanin nano-delivery system (FSHANPs) capable of visualizing inflammation-targeting sites and programmed release of anthocyanins in response to ROS surging from reactive lesion sites. FSHANPs are composed of abundant active functional groups on the surface of foodborne nanoparticles nano-self-assembled with alginate, hyaluronic acid, and anthocyanins. Alginate provided effective protection against enzyme degradation in the gastrointestinal tract of these anthocyanin molecules. The accumulation of FSHANPs at the site of the inflamed colon in IBD was contingent upon the fluorescence characteristics of the nanoparticles, which was subsequently followed by the specific recognition of the overexpressed CD44 protein by hyaluronic acid. Thus, facilitating the precise and targeted delivery of anthocyanins at the inflammatory site. Mechanically, FSHANPs containing anthocyanins effectively impeded the damage caused by ROS damage in RAW264.7 cells, alleviated lipopolysaccharide-induced apoptosis, and prevented the decline of mitochondrial membrane potential (p < 0.001). Additionally, the administration of FSHANPs reduced the expression of inflammatory factors, restored IBD-induced weight loss symptoms, and shortened colons due to the treatment with sodium dextran sulfate. Further studies showed that FSHANPs expedited intestinal mucosal healing and altered intestinal microbiota composition with increased abundance of beneficial bacteria such as Firmicutes and Muribaculaceae (p < 0.05). In conclusion, this study presents a promising therapy for IBD and a potential target for other inflammatory diseases, which can precisely deliver antioxidants into inflamed colon sites with oxidative stress-responsive and visualizing effects.

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