文献类型：期刊文献

英文题名：Effective and safe delivery of GLP-1AR and FGF-21 plasmids using amino-functionalized dual-mesoporous silica nanoparticles in vitro and in vivo

作者：Geng, Shan[1];Qin, Limei[2];He, Yirui[1];Li, Xinrun[1];Yang, Mengliu[1];Li, Ling[1];Liu, Dongfang[1];Li, Yongsheng[2];Niu, Dechao[2];Yang, Gangyi[1]

机构：[1]Chongqing Med Univ, Affiliated Hosp 2, Dept Endocrinol, Chongqing 400010, Peoples R China;[2]East China Univ Sci & Technol, Sch Mat Sci AndEngn, Lab Low Dimens Mat Chem, Shanghai 200237, Peoples R China

年份：2021

卷号：271

外文期刊名：BIOMATERIALS

收录：;EI(收录号：20211310140078);WOS:【SCI-EXPANDED(收录号:WOS:000639792100002)】；

基金：This work was supported by grants from National Natural Science Foundation (No. 81500666 and 52072124), and the Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning).

语种：英文

外文关键词：Insulin resistance; GLP-1AR; FGF-21; Dual-mesoporous silica nanoparticles

摘要：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 (similar to 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.