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Developing glycan-nanoparticles for specific DC-SIGN targeting and dendritic cell immune modulation via picodroplet single cell analysis

通过微微滴单细胞分析开发用于特定 DC-SIGN 靶向和树突状细胞免疫调节的聚糖纳米颗粒

基本信息

批准号：
2601051
负责人：
金额：
--
依托单位：
University of Leeds
依托单位国家：
英国
项目类别：
Studentship
财政年份：
2021
资助国家：
英国
起止时间：
2021 至无数据
项目状态：
未结题

来源：
https://gtr.ukri.org/projects?ref=studentship-2601051
关键词：
Developing glycan nanoparticles specific DC

项目摘要

Multivalent protein-sugar interactions (PSIs) are widespread and widely exploited by viruses and cancer cells to modulate host immunity to aid infection and/or cancer development.[1] The underlying structural, molecular and cellular mechanisms remain unclear. This EPSRC industrial CASE project aims to develop novel glycan-nanoparticles and their assemblies to mimic virus-dendritic cell (DC) interactions. We will design and synthesis different size and shape gold nanoparticle and coat them with specific lipoic acid-oligo(ethylene glycol)-based multifunctional glycan ligands.[2] By tuning the glycan valency, inter-glycan spacing, scaffold size and shape, and assembly state, we aim to establish the design rules for targeting specific PSIs for DC immune function modulation. We will probe the glycan-nanoparticle-DC interactions via the state-of-art high throughput picodroplet technology [3] recently developed by Sphere Fluidics Ltd, our industrial partner. We will further harness this new capability to develop novel therapeutic treatments against viral infection and cancer.[4]Reference: [1] Banchereau & Steinman, Nature, 1998, 392, 245; [2] Guo et al. J. Am Chem. Soc. 2017, 139, 11833; Budhadev et al. J. Am Chem. Soc. 2020, 142, 18022. [3] Josephides et al. SLAS Technol., 2020, 25, 177. [4] Palucka & Banchereau, Nature Rev. Cancer, 2012, 12, 265.

多价蛋白-糖相互作用（PSI）是广泛存在的，并且被病毒和癌细胞广泛利用来调节宿主免疫力以帮助感染和/或癌症发展。[1]其潜在的结构、分子和细胞机制仍不清楚。这个EPSRC工业CASE项目旨在开发新型聚糖纳米颗粒及其组装体，以模拟病毒-树突状细胞（DC）相互作用。我们将设计并合成不同大小和形状的金纳米粒子，并在其表面包覆特定的基于硫辛酸-寡聚（乙二醇）的多功能聚糖配体。[2]通过调整聚糖价态、聚糖间间距、支架尺寸和形状以及组装状态，我们的目标是建立靶向DC免疫功能调节的特异性PSI的设计规则。我们将通过我们的工业合作伙伴Sphere Fluidics Ltd最近开发的最先进的高通量picodroplet技术[3]探测聚糖-纳米颗粒-DC相互作用。我们将进一步利用这一新能力，开发针对病毒感染和癌症的新型治疗方法。[4]参考文献：[1] Banchereau & Steinman，Nature，1998，392，245; [2] Guo等人，J. Am Chem. Soc. 2017，139，11833; Budhadev等人，J. Am Chem. Soc. 2020，142，18022。[3]Josephides等人，SLAS Technol.，2020年第25期第177期[4]Palucka和Banchereau，Nature Rev. Cancer，2012，12，265.