Harnessing β-glucan conjugated quercetin nanocomplex to function as a promising anti-inflammatory agent via macrophage-targeted delivery.

Quercetin, a promising anti-inflammatory agent, faces challenges related to poor bioavailability and limited practical applications. β-glucan, a natural polysaccharide, can be specifically recognized by macrophages, making it an ideal targeting carrier to enhance therapeutic efficacy for macrophage-related dysfunctions. In this study, β-glucan conjugated quercetin nano-complexes (CM-Cur@QT) were developed to target macrophage and alleviate pro-inflammatory response in M1-like macrophages. The results demonstrated that CM-Cur@QT exhibited a spheric shape with an average diameter around 200 nm. FT-IR, H NMR, XRD and XPS analyses confirmed the complexation of CM-Cur@QT. This complex showed excellent stability during stimulated digestion, protecting QT from degradation while maintaining favorable antioxidant activity. After complexation, CM-Cur@QT displayed sustained uptake kinetics and enhanced accumulation in macrophages, with a 61.88 % increase compared to individual quercetin after 5 h of incubation. Meanwhile, CM-Cur@QT administration induced evidently cell cycle phases transitions and altered phagocytotic activity in M1-like macrophages. Furthermore, CM-Cur@QT reduced intracellular ROS accumulation, achieving a ROS scavenging rate of up to 49.92 %, compared to 25.59 % in quercetin group. This complex also effectively modulated TNF-a, IL-6 and TGF-β secretion profiles in pro-inflammatory macrophages, outperforming individual QT treatment. Notably, CM-Cur@QT facilitated anti-inflammatory effects while minimizing impacts on inactivated M0 macrophages. These findings underscore the potential of CM-Cur@QT as a promising agent for mitigating inflammatory disorders.