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http://hdl.handle.net/1942/38704
Title: | Polymer-tethered glycosylated gold nanoparticles recruit sialylated glycoproteins into their protein corona, leading to off-target lectin binding | Authors: | Ahmad , Ashfaq Georgiou, Panagiotis G. PANCARO, Alessia Hasan, Muhammad Nelissen, Inge Gibson, Matthew, I |
Issue Date: | 2022 | Publisher: | ROYAL SOC CHEMISTRY | Source: | Nanoscale, 14 (36) , p. 13261 -13273 | Abstract: | Upon exposure to biological fluids, the fouling of nanomaterial surfaces results in non-specific capture of proteins, which is particularly important when in contact with blood for in vivo and ex vivo applications. It is crucial to evaluate not just the protein components but also the glycans attached to those proteins. Polymer-tethered glycosylated gold nanoparticles have shown promise for use in biosensing/diagnostics, but the impact of the glycoprotein corona has not been established. Here we investigate how polymer-tethered glycosylated gold nanoparticles interact with serum proteins and demonstrate that the protein corona introduces new glycans and hence off-specific targeting capability. Using a panel of RAFT-derived polymers grafted to the gold surface, we show that the extent of corona formation is not dependent on the type of polymer. In lectin-binding assays, a glycan (galactose) installed on the chain-end of the polymer was available for binding even after protein corona formation. However, using sialic-acid binding lectins, it was found that there was significant off-target binding due to the large density of sialic acids introduced in the corona, confirmed by western blotting. To demonstrate the importance, we show that the nanoparticles can bind Siglec-2, an immune-relevant lectin post-corona formation. Pre-coating with (non-glycosylated) bovine serum albumin led to a significant reduction in the total glycoprotein corona. However, sufficient sialic acids were still present in the residual corona to lead to off-target binding. These results demonstrate the importance of the glycans when considering the protein corona and how 'retention of the desired function' does not rule out 'installation of undesired function' when considering the performance of glyco-nanomaterials. | Notes: | Gibson, MI (corresponding author), Univ Warwick, Dept Chem, Gibbet Hill Rd, Coventry CV4 7AL, W Midlands, England.; Gibson, MI (corresponding author), Univ Warwick, Warwick Med Sch, Div Biomed Sci, Gibbet Hill Rd, Coventry CV4 7AL, W Midlands, England. m.i.gibson@warwick.ac.uk |
Keywords: | Galactose;Glycoproteins;Gold;Lectins;Polymers;Polysaccharides;Protein Binding;Serum Albumin, Bovine;Sialic Acid Binding Ig-like Lectin 2;Sialic Acids;Metal Nanoparticles;Nanoparticles;Protein Corona | Document URI: | http://hdl.handle.net/1942/38704 | ISSN: | 2040-3364 | e-ISSN: | 2040-3372 | DOI: | 10.1039/d2nr01818g | ISI #: | 000848869100001 | Rights: | The Royal Society of Chemistry 2022. Open access This article is licensed under a Creative Commons Attribution 3.0 Updated licence | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2023 |
Appears in Collections: | Research publications |
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d2nr01818g 13261..13273 ++.pdf | Published version | 4.13 MB | Adobe PDF | View/Open |
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