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

宋莹莹; 葛玮; 董常明

doi:10.11777/j.issn1000-3304.2023.23069

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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

研究论文 | 更新时间：2023-09-25

- 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
  增强出版
- Glycosylated Polypeptide Nanovesicles: Fabrication, Protein and Agonist Codelivery and Immune Activity
- 高分子学报 2023年54卷第10期页码：1533-1546
- 作者机构：
  
  上海交通大学化学化工学院上海 200240
- 作者简介：
  
  E-mail: cmdong@sjtu.edu.cn
- 基金信息：
  
  国家自然科学基金(基金号 22075176);上海市自然基金(基金号 22ZR1429200)
- DOI：10.11777/j.issn1000-3304.2023.23069
  中图分类号：
- 纸质出版日期：2023-10-20，
  
  网络出版日期：2023-07-04，
  
  收稿日期：2023-03-23，
  
  录用日期：2023-04-28
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宋莹莹,葛玮,董常明.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[J].高分子学报,2023,54(10):1533-1546.

Song Ying-ying,Ge Wei,Dong Chang-ming.Glycosylated Polypeptide Nanovesicles: Fabrication, Protein and Agonist Codelivery and Immune Activity[J].ACTA POLYMERICA SINICA,2023,54(10):1533-1546.
宋莹莹,葛玮,董常明.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[J].高分子学报,2023,54(10):1533-1546. DOI： 10.11777/j.issn1000-3304.2023.23069.

Song Ying-ying,Ge Wei,Dong Chang-ming.Glycosylated Polypeptide Nanovesicles: Fabrication, Protein and Agonist Codelivery and Immune Activity[J].ACTA POLYMERICA SINICA,2023,54(10):1533-1546. DOI： 10.11777/j.issn1000-3304.2023.23069.

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.

Abstract

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-‍

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-‍

remarkably 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 strong immune response. Consequently

this work opens a new avenue to construct the immune cells-targeted biodegradable nanocarriers for delivering antigens and agonists to fight against infectious diseases and cancers.

关键词

糖聚肽纳米囊泡蛋白递送激动剂免疫佐剂

Keywords

GlycopolypeptideNanovesicleProtein deliveryAgonistImmune adjuvant

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