College of Animal Husbandry and Veterinary Medicine, Southwest Minzu University, Chengdu, Sichuan 610041, PR China; Key Laboratory of Ministry of Education and Sichuan Province for Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Chengdu, Sichuan 610041, PR China.
College of Animal Husbandry and Veterinary Medicine, Southwest Minzu University, Chengdu, Sichuan 610041, PR China; Key Laboratory of Ministry of Education and Sichuan Province for Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization, Chengdu, Sichuan 610041, PR China.
Int J Biol Macromol. 2023 Jan 1;224:998-1011. doi: 10.1016/j.ijbiomac.2022.10.184. Epub 2022 Oct 25.
Potentilla anserina L polysaccharide (PAP) is known to regulate immunity. Poly(lactic-co-glycolicacid) (PLGA) is a type of drug carrier with biocompatibility and biodegradable USFDA approved polymer, which possesses the advantages of high safety and good sustained-release effect. The DEC205 receptor, a type I membrane protein, is widely distributed on the surface of macrophages and dendritic cells (DCs) and plays a key role in antigen recognition and presentation. In this study, we prepared Potentilla anserina L polysaccharide PLGA nanoparticles targeting DEC205 receptor (DEC205-PAPP) and characterized the nanoparticles with regards to their effects on immune activation in vitro and in vivo. In vitro, DEC205-PAPP promoted the uptake activity of macrophages and increased the secretion of NO and cytokines (IFN-γ, IL-4, IL-6, and GM-CSF), up-regulated the expression of CD80, CD86. In vivo, DEC205-PAPP elevated the immune organ index, induced DC maturation, promoted T lymphocyte proliferation and differentiation, and increased the levels of antigen-specific IgG antibody and cytokines (IFN-γ, IL-4), which prolonged the residence time of the OVA antigen in the immune organs and the lymph nodes. In conclusion, DEC205-PAPP had a slow-release effect, induced humoral and cellular immune responses, and could potentially be used as an effective antigen-targeted delivery system.
鹅绒委陵菜多糖(PAP)已被证实具有调节免疫的作用。聚乳酸-羟基乙酸共聚物(PLGA)是一种具有生物相容性和可生物降解性的药物载体,已获得美国食品药品监督管理局(USFDA)批准,其优点在于安全性高、缓释效果好。DEC205 受体是一种 I 型跨膜蛋白,广泛分布于巨噬细胞和树突状细胞(DC)表面,在抗原识别和呈递中发挥关键作用。在本研究中,我们制备了靶向 DEC205 受体的鹅绒委陵菜多糖 PLGA 纳米粒(DEC205-PAPP),并对其在体外和体内的免疫激活作用进行了特征描述。体外实验结果表明,DEC205-PAPP 可促进巨噬细胞的摄取活性,增加 NO 和细胞因子(IFN-γ、IL-4、IL-6 和 GM-CSF)的分泌,上调 CD80 和 CD86 的表达。体内实验结果表明,DEC205-PAPP 可提高免疫器官指数,诱导 DC 成熟,促进 T 淋巴细胞增殖和分化,并增加抗原特异性 IgG 抗体和细胞因子(IFN-γ、IL-4)的水平,延长 OVA 抗原在免疫器官和淋巴结中的驻留时间。总之,DEC205-PAPP 具有缓释作用,可诱导体液和细胞免疫应答,有望成为一种有效的抗原靶向递送系统。