Activation of human Natural Killer cells by graphene oxide-templated antibody nanoclusters

Christian Loftus, Mezida Saeed, Daniel M Davis, Iain E. Dunlop

Research output: Contribution to journalArticlepeer-review

Abstract

An emerging new paradigm is that immune cell activation is controlled by transient interactions between supramolecular assemblies of receptors and ligands. Current immunotherapy biologic pharmaceuticals that activate or desensitize NK cells are, however, individual molecules that do not replicate this nanoscale organization of proteins. Here, we use nanoscale graphene oxide
(NGO) as a template to generate soluble nanoscale clusters of Natural Killer cell-activating antibodies. We control nanocluster size and molecular number to mimic reported values for cell surface proteins. These NGO-templated molecular nanoclusters, used to stimulate NK cells via the CD16 receptor, successfully induced cellular activation, indicated by degranulation of cytolytic granules and IFN-g secretion. Importantly, activation significantly exceeded that induced by the same antibodies applied as a solution of individual molecules. These results
demonstrate that future immunotherapies could be enhanced by assembling
immunomodulatory drugs into nanoclusters, and establish NGO-templating as a candidate technology.
Original languageEnglish
Pages (from-to)3282-3289
JournalNano Letters
Volume18
Issue number5
Early online date20 Apr 2018
DOIs
Publication statusPublished - 9 May 2018

Keywords

  • bionanotechnology
  • biofunctional nanoparticles
  • graphene oxide
  • NK cell
  • immune cell activation

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