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

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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.