糖基化聚肽纳米囊泡的构筑、蛋白和激动剂共递送及免疫活性  

Glycosylated Polypeptide Nanovesicles: Fabrication, Protein and Agonist Codelivery and Immune Activity

作　　者：宋莹莹 葛玮 董常明 Ying-ying Song;Wei Ge;Chang-ming Dong(School of Chemistry and Chemical Engineering,Shanghai Jiao Tong University,Shanghai 200240)

机构地区：[1]上海交通大学化学化工学院,上海200240

出　　处：《高分子学报》2023年第10期1533-1546,共14页Acta Polymerica Sinica

基　　金：国家自然科学基金(基金号22075176);上海市自然基金(基金号22ZR1429200)资助项目.

摘　　要：为构建兼具细胞靶向和免疫活性的生物降解聚合物纳米载体,报道了3种糖基修饰的线形聚肽-含糖树枝化共聚物构筑的纳米囊泡及在蛋白抗原和免疫激动剂共递送载体中的应用.通过透析法制备了共负载卵清蛋白(OVA)和免疫激动剂咪喹莫特(R837)的糖聚肽纳米囊泡(PNLys-4Man、PNLys-4Gal、PNLys-4Glu),显示出糖基依赖性的促进树突状细胞(DC)熟化的免疫佐剂效应,且甘露糖修饰的纳米囊泡具有靶向DC细胞而增强的免疫活性;施加紫外光促使OVA和R837胞内快速释放,显著提高了DC细胞熟化和免疫相关共刺激因子的分泌水平,说明糖聚肽纳米囊泡及OVA抗原、R837激动剂具有协同促进DC细胞熟化的免疫活性.Most of polymeric vesicles not only lack the specific recognitions of immune cells and the bioactivities of adjuvants to trigger efficient adaptive immunities,but also lack good biodegradability and biocompatibility,which hamper the immunotherapy applications.To develop biodegradable polymer nano-carries with both immune activity and cell-targeting,three kinds of glycopolypeptide nanovesicles constructed by linear polypeptide-glycodendrimer copolymers were synthesized and the applications in co-delivery of protein antigens and agonists were studied.The glycopolypeptide nanovesicles(PNLys-4Man,PNLys-4Gal,PNLys-4Glu)were fabricated in aqueous solution by a dialysis method,which had similar sugar density,hydrodynamic size of about 100 nm and Zeta potential of about 35 mV,and present sugar-dependent recognition with lectins.Those glycopolypeptide vesicles could co-load ovalbumin(OVA)and imiquimote(R837)in phosphate buffer solution(pH=7.4)to give a hydrodynamic size of about 75 nm,and the loading capacity of OVA and R837 was about 7.5%and about 1.3%,respectively.Moreover,those vesicles showed sugar-dependent adjuvant effects of promoting dendritic cell(DCs)maturation,in which the mannosylated ones enhanced the maturation of DCs to 34.6%compared to the galactosylated ones of 29.4%and the glucosylated ones of 27.7%.These data evidence that the mannosylated glycopolypeptide vesicles exhibited a cell-targeting enhanced immunity.Furthermore,the mannosylated nanovesicles activated the maturation of DCs to secret costimulatory molecules of IL-6 and TNF-α,and their levels were respectively enhanced by 19.5%and 20.3%than the galactosylated ones,and by 17.7%and 37.4%than the glucosylated ones,further confirming the sugar-dependent maturation effect on DCs.Especially,UV light triggered intracellular rapid co-release of OVA and R837,and the levels of IL-6 and TNF-αremarkably enhanced by 2.19-fold and 1.82-fold,demonstrating that OVA antigen and R837 agonist possessed synergistic effect to promote DCs maturation and induce stron

关 键 词：糖聚肽 纳米囊泡 蛋白递送 激动剂 免疫佐剂 

分 类 号：TQ460.1[化学工程—制药化工] O636[理学—高分子化学]