Effective and safe delivery of GLP-1AR and FGF-21 plasmids using amino-functionalized dual-mesoporous silica nanoparticles in vitro and in vivo. (April 2021)

• Record Type: Journal Article
• Authors: Geng, Shan; Qin, Limei; He, Yirui; Li, Xinrun; Yang, Mengliu; Li, Ling; Liu, Dongfang; Li, Yongsheng; Niu, Dechao; Yang, Gangyi
• Is Part Of: Biomaterials. Volume 271(2021)
• Publication Date: 2021-04
• Subjects: Insulin resistance -- GLP-1AR -- FGF-21 -- Dual-mesoporous silica nanoparticles; Biomedical materials -- Periodicals; Biocompatible Materials -- Periodicals; Biomatériaux -- Périodiques; 610.28
• DOI: 10.1016/j.biomaterials.2021.120763
• Languages: English
• ISSNs: 0142-9612

Abstract

Abstract: Nanomaterials have attracted increased attention because of their excellent drug-carrying capacity. However, these nanomaterials are rarely used in the treatment of metabolic diseases. Liraglutide, a glucagon-like peptide-1 receptor agonist, has been widely used in the treatment of type 2 diabetes mellitus (T2DM). Furthermore, fibroblast growth factor 21 (FGF-21) has been found to improve glucose metabolism and insulin resistance (IR). To investigate whether these two molecules have synergistic effects in vivo, we developed a novel drug delivery system using amino-functionalized and embedded dual-mesoporous silica nanoparticles (N-EDMSNs) to simultaneously carry liraglutide and FGF-21, and observed their biological effects. The resultant N-EDMSNs possessed unique hierarchical porous structures consisting of open large pores (>10 nm) and small mesopores (~2.5 nm) in the silica framework, highly positively charged surfaces and good disperisity in aqueous solution. We found that N-EDMSNs had a high loading capacity for exogenous genes and low toxicity to Hepa1-6 cells. Moreover, N-EDMSNs can simultaneously carry FGF-21 plasmids and liraglutide and successfully transfect them into Hepa1-6 cells. The transfection efficiency of N-EDMSNs was higher than that of Lipofectamine 2000 in vitro. In mice experiments, N-EDMSNs/pFGF21 treatment resulted in higher FGF-21 expression in the liver than pFGF21 treatment with hydrodynamic delivery. Compared with both pFGF21 and liraglutide, N-EDMSNs/pFGF21/Lira treatment significantly reduced the food intake, body weight, and blood glucose; increased the energy expenditure and improved hepatic IR in high-fat diet (HFD)-fed mice. Our results demonstrated that the biological effects of N-EDMSNs/pFGF21/Lira complexes were better than those of pFGF21 combined with liraglutide in vivo.