Ahmad, Ashfaq, Georgiou, Panagiotis G., Pancaro, Alessia, Hasan, Muhammad, Nelissen, Inge and Gibson, Matthew I. (2022) Polymer-tethered glycosylated gold nanoparticles recruit sialylated glycoproteins into their protein corona, leading to off-target lectin binding. Nanoscale . doi:10.1039/D2NR01818G ISSN 2040-3364. [ 🗎 Public]. [ (✓) hoa:511 ] (In Press)

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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.

Item Type:	Journal Article
Subjects:	Q Science > QD Chemistry Q Science > QP Physiology T Technology > TA Engineering (General). Civil engineering (General)
Divisions:	Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences Faculty of Science, Engineering and Medicine > Science > Chemistry Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Nanostructured materials , Nanostructured materials -- Surfaces, Glycoproteins -- Synthesis , Addition polymerization , Lectins
Journal or Publication Title:	Nanoscale
Publisher:	Royal Society of Chemistry
ISSN:	2040-3364
Official Date:	2022
Dates:	Date Event 2022 Published 30 August 2022 Available 23 August 2022 Accepted 1 April 2022 Submitted
DOI:	10.1039/D2NR01818G
Status:	Peer Reviewed
Publication Status:	In Press
Access rights to Published version:	Open Access (Creative Commons)
Date of first compliant deposit:	13 September 2022
Date of first compliant Open Access:	14 September 2022
RIOXX Funder/Project Grant:	Project/Grant ID RIOXX Funder Name Funder ID 866056 [ERC] Horizon 2020 Framework Programme http://dx.doi.org/10.13039/100010661 814236 H2020 Marie Skłodowska-Curie Actions http://dx.doi.org/10.13039/100010665

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