• Graphene Oxide Nanosheets Interact and Interfere with SARS‐CoV‐2 Surface Proteins and Cell Receptors to Inhibit Infectivity

      Unal, Mehmet Altay; Bayrakdar, Fatma; Nazir, Hasan; Besbinar, Omur; Gurcan, Cansu; Lozano, Neus; Arellano, Luis M.; Yalcin, Süleyman; Panatli, Oguzhan; Celik, Dogantan; et al. (2021-05-14)
      Abstract: Nanotechnology can offer a number of options against coronavirus disease 2019 (COVID‐19) acting both extracellularly and intracellularly to the host cells. Here, the aim is to explore graphene oxide (GO), the most studied 2D nanomaterial in biomedical applications, as a nanoscale platform for interaction with SARS‐CoV‐2. Molecular docking analyses of GO sheets on interaction with three different structures: SARS‐CoV‐2 viral spike (open state – 6VYB or closed state – 6VXX), ACE2 (1R42), and the ACE2‐bound spike complex (6M0J) are performed. GO shows high affinity for the surface of all three structures (6M0J, 6VYB and 6VXX). When binding affinities and involved bonding types are compared, GO interacts more strongly with the spike or ACE2, compared to 6M0J. Infection experiments using infectious viral particles from four different clades as classified by Global Initiative on Sharing all Influenza Data (GISAID), are performed for validation purposes. Thin, biological‐grade GO nanoscale (few hundred nanometers in lateral dimension) sheets are able to significantly reduce copies for three different viral clades. This data has demonstrated that GO sheets have the capacity to interact with SARS‐CoV‐2 surface components and disrupt infectivity even in the presence of any mutations on the viral spike. GO nanosheets are proposed to be further explored as a nanoscale platform for development of antiviral strategies against COVID‐19.
    • The impact of graphene oxide sheet lateral dimensions on their pharmacokinetic and tissue distribution profiles in mice.

      Jasim, Dhifaf A; Newman, Leon; Rodrigues, Artur Filipe; Vacchi, Isabella A; Lucherelli, Matteo A; Lozano, Neus; Ménard-Moyon, Cécilia; Bianco, Alberto; Kostarelos, Kostas; email: kostas.kostarelos@manchester.ac.uk (2021-08-18)
      Although the use of graphene and 2-dimensional (2D) materials in biomedicine has been explored for over a decade now, there are still significant knowledge gaps regarding the fate of these materials upon interaction with living systems. Here, the pharmacokinetic profile of graphene oxide (GO) sheets of three different lateral dimensions was studied. The GO materials were functionalized with a PEGylated DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid), a radiometal chelating agent for radioisotope attachment for single photon emission computed tomography (SPECT/CT) imaging. Our results revealed that GO materials with three distinct size distributions, large (l-GO-DOTA), small (s-GO-DOTA) and ultra-small (us-GO-DOTA), were sequestered by the spleen and liver. Significant accumulation of the large material (l-GO-DOTA) in the lungs was also observed, unlike the other two materials. Interestingly, there was extensive urinary excretion of all three GO nanomaterials indicating that urinary excretion of these structures was not affected by lateral dimensions. Comparing with previous studies, we believe that the thickness of layered nanomaterials is the predominant factor that governs their excretion rather than lateral size. However, the rate of urinary excretion was affected by lateral size, with large GO excreting at slower rates. This study provides better understanding of 2D materials behaviour with different structural features in vivo. [Abstract copyright: Copyright © 2021. Published by Elsevier B.V.]