Harnessing Β-Glucan Conjugated Quercetin Nanocomplex to Function as a Promising Anti-Inflammatory Agent Via Macrophage-Targeted Delivery

As a promising anti-inflammatory agent, quercetin faces challenges of limited bioavailability and practical application. β-glucan, a natural polysaccharide, can be recognized specifically by macrophages, making it an ideal targeting carrier to enhance therapeutic efficacy for macrophage-related dysfunctions. In this study, we developed β-glucan conjugated quercetin nano-complexes (CM-Cur@QT) and evaluate their potential of macrophage-targeted delivery and anti-inflammation on M1-like macrophages. Our results demonstrate that CM-Cur@QT exhibit a spheric shape with an average diameter around 200 nm and FT-IR, 1H NMR, XRD and XPS analysis were confirmed their complexation. The nano-complexes showed excellent stability during stimulated digestive process, protecting QT from degradation while maintaining antioxidant activity. After complexation, CM-Cur@QT displayed prolonged uptake kinetics and enhanced macrophages accumulation. Notably, CM-Cur@QT administration induced evidently cell cycle phases transitions and altered phagocytotic activity in M1-like macrophages, suggesting potential phenotype repolarization Furthermore, CM-Cur@QT alleviated intracellular ROS accumulation and modulated TNF-a, IL-6 and TGF- β secretion profiles in pro-inflammatory macrophages, outperforming individual QT and CM-Cur treatments. Additionally, CM-Cur@QT not only facilitated anti-inflammatory effects compared to individual QT treatment but also minimized impacts on inactivated M0 macrophages. These findings underscore the potential of CM-Cur@QT as an effective strategy for mitigating inflammatory disorders.