Mannose-rich Oligosaccharides-functionalized selenium nanoparticles mediates Macrophage reprogramming and inflammation resolution in ulcerative colitis

Inflammatory bowel disease (IBD) is a global disease and usually classified into Crohn's disease (CD) and ulcerative colitis (UC), in which the inflammatory response is known to play a pivotal role. Herein, a bioactive component of mannose-rich oligosaccharides (MRO) was produced by enzymatic hydrolysis with most potent anti-inflammation and employed to functionalize selenium nanoparticles (SeNPs), aming to solve of inflammation in UC by accelerating the reprogramming of macrophages. In this study, SeNPs was prepared by selenite and MRO with ascorbic acid reduction. The stability and biocompatibility of SeNPs was obviously improved by the functionalization of MRO, resulting in spheres (2 mu M Se) carrying around 26 ng/ml MRO (MRO-SeNPs) with an average diameter of 70 nm remained stable in 60 d. In addition, efficient cellular uptake of MRO-SeNPs in macrophages was detected by contribution of MRO targeted to the receptors of macrophages. As expected, MROSeNPs exhibited improvement of macrophage reprogramming in vitro, thus leading to a typical M2 polarization profile of cytokine expression. Furthermore, in DSS-induced mouse colitis model, MRO-SeNPs effectively mitigated colitis by suppressing the pro-inflammatory such as IL-1 beta, IL-6, TNF-alpha, IL-12 and MCP-1 cytokines in situ, and exerted salient antioxidant capacity in colon tissues. As a result, MRO-SeNPs exhibited therapeutic potential by promoting macrophages reprogramming leading to inflammation resolution. Taken together, this study not only provides strategy for functionalization of nanomedicines using structure-optimized MRO, but also reveals the action mechanism on successful treatment of IBD and other intestinal diseases.

Automated summary

In this study, a bioactive component of mannose-rich oligosaccharides (MRO) was produced and used to functionalize selenium nanoparticles (SeNPs) in order to reprogram macrophages and mitigate inflammation in inflammatory bowel disease (IBD). The MRO-functionalized SeNPs showed improved stability and biocompatibility, and effectively suppressed pro-inflammatory cytokines in a mouse colitis model. This study not only provides a strategy for functionalizing nanomedicines, but also reveals the mechanism of successful treatment of IBD and other intestinal diseases.