Chiral Selenium Nanotherapeutics Regulates Selenoproteins to Attenuate Glucocorticoid‐Induced Osteoporosis. (13th February 2023)

• Record Type: Journal Article
• Authors: Xiong, Zushuang; Lin, Hao; Li, Hong; Zou, Binghua; Xie, Bin; Yu, Yanzi; He, Lizhen; Chen, Tianfeng
• Is Part Of: Advanced functional materials. Volume 33:Number 17(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2023-02-13
• Subjects: chiral selenium nanoparticles -- dexamethasone -- fatty liver formation -- glucocorticoid‐induced osteoporosis -- selenoproteins -- stereoselectivity; Materials -- Periodicals; Chemical vapor deposition -- Periodicals; 620.11
• DOI: 10.1002/adfm.202212970
• Languages: English
• ISSNs: 1616-301X

Abstract

Abstract: Glucocorticoid (GC)‐induced osteoporosis (GIO) is a concurrent disease commonly appeared in chronic inflammatory and autoimmune disease patients. Stereoselective recognition between chiral drugs and homochiral biological molecules could directly affect their distribution, adhesion and transport. Herein, trace element selenium (Se) with bone formation‐regulating activity, is employed to construct cysteine‐decorated chiral nanoparticles (Cys@SeNPs) to attenuate GIO. Interestingly, comparing with the racemic (DL‐Cys@SeNPs) and D‐Cys@SeNPs, the L‐Cys@SeNPs displays higher uptake in osteoblast cells and could lessen reactive oxygen species overproduction to block dexamethasone (Dex)‐induced osteoblasts cells apoptosis. Intracellular L‐Cys@SeNPs could be predominantly transformed to selenocystine to upregulate the expression levels of antioxidative selenoproteins to effectively scavenge Dex‐induced excessive ROS accumulation in osteoblasts, and thus reduce the undesirable apoptosis through activating Wnt/β‐catenin pathway. Consistently, L‐Cys@SeNPs significantly alleviates the main osteoporosis symptoms of bone trabeculae destruction and decreased bone density in vivo, and also reduces the weight gain and fatty liver formation in Dex‐exposed mice, thus suppressing the overall side effects of Dex. This study not only demonstrates an effective strategy for treatment of GIO by using chiral Se nanomedicine, but also elucidates the important roles of selenoproteins in alleviating osteoporosis, which could help for future Se‐based drug design through chirality control engineering. Abstract : Selenium atom is engineered to synthesize chiral selenium nanoparticles to overcome glucocorticoid‐induced osteoporosis. This nanotherapeutics can be predominantly transformed to selenocystine and selenocysteine and upregulate selenoproteins, which effectively scavenges dexamethasone‐induced reactive oxygen species overproduction in osteoblasts and blocks undesirable cell apoptosis through activating Wnt/β‐catenin pathway. Resultantly, selenium nanoparticles reduce the dexamethasone‐induced osteoporosis symptoms and suppress the overall side effects.