Self-assembly of selenium-loaded octenyl succinic anhydride-modified starch nanomicelles for treating inflammation-related brain diseases

•FA-OSAS-SeNPs shows good physiological stability and excellent biocompatibility.•FA-OSAS-SeNPs alleviates cognitive deficits in LPS-induced mice.•FA-OSAS-SeNPs reduces neuroinflammation and endoplasmic reticulum stress.•FA-OSAS-SeNPs exert potent anti-inflammatory effects through multiple pathways. Neuroinflammation, caused by abnormal activation of glial cells, plays an important role in nerve injury, which can lead to cognitive impairment. Consequently, regulating glial cell activation and subsequent generation of inflammatory mediators is valuable for the treatment of neuroinflammation-based brain diseases. Selenium (Se) and folic acid (FA) are two key nutritional supplements that have bioactivities associated with regulating neuroinflammatory responses, resisting oxidative stress, and preventing neuronal apoptosis in vivo. Based on this, we prepared multifunctional nanoparticles using octenyl succinic anhydride (OSA)-modified starch (OSAS) to carry both Se and FA, with the aim to facilitate synergistic resistance of neuroinflammatory diseases. The FA-grafted OSAS molecules self-assembled into nanomicelles and functioned as nanocarriers to load selenium nanoparticles (SeNPs) (a unique form of Se supplement) and form novel nanoparticles FA-OSAS-SeNPs with a protective shell of starch. Furthermore, the effect and mechanism of FA-OSAS-SeNPs on inflammatory responses were investigated using lipopolysaccharide (LPS)-induced BV2 microglial cells and BALB/c mice. Our results showed that FA-OSAS-SeNPs ameliorated LPS-induced spatial learning and memory impairment. Furthermore, FA-OSAS-SeNPs significantly suppressed the activation of glial cells, the expression of oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and the release of inflammatory factors. Moreover, FA-OSAS-SeNPs prominently alleviated endoplasmic reticulum (ER) stress and LPS-induced overactivation of the NF-κB and MAPK signaling pathways. In conclusion, these results demonstrate that FA-OSAS-SeNPs represent a promising candidate in alternative/supplementary medication or functional foods for treating inflammatory brain diseases.