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Activation of Human Natural Killer Cells by Graphene Oxide-Templated Antibody Nanoclusters.

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-? 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.

SUBMITTER: Loftus C

PROVIDER: S-EPMC5951604 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Activation of Human Natural Killer Cells by Graphene Oxide-Templated Antibody Nanoclusters.

Loftus Christian C Saeed Mezida M Davis Daniel M DM Dunlop Iain E IE

Nano letters 20180420 5

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 nanoclu ...[more]

PMID: 29676151

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Project description:Bombyx mori silk fibroin (SF) is a promising natural biocompatible protein. However, its interaction with graphene oxide (GO) has never been studied and the resultant SF/GO matrix has not been used to direct stem cell fate. Herein, we found out that mixing SF molecules and GO nanosheets in an aqueous solution can trigger the assembly of SF nanoparticles into oriented nanofibrils due to the guidance of GO nanosheets, forming SF/GO films with unique nanotopographies and improved modulus upon the removal of the solvent. When GO mass percentage in the SF/GO films is 2 and 10%, the SF assemblies are necklace-like nanofibrils (assembled from loosely linked SF nanoparticles) and solid nanofibrils (assembled from densely linked SF nanoparticles) in the resultant films, termed SG2 and SG10, respectively. GO nanosheets guided the SF assembly into nanofibrils by triggering the structural change of SF molecules from random coils to ?-sheets, as confirmed by Fourier transform infrared spectroscopy and circular dichroism measurements. Furthermore, oxidative groups in the GO nanosheets were reduced by the reducing groups in SF during the nanofibril formation according to X-ray photoelectron spectroscopy and Raman spectroscopy. The reduction of the oxidative groups in GO by SF was further verified by the good cell viability on the SF/GO films. The unique nanotopographies of the SF/GO films were found to accelerate the early cell adhesion and induce the osteogenic differentiation of human mesenchymal stem cells (MSCs) even in the absence of additional inducers in the medium. More importantly, SG10 presents a stronger capability in promoting early MSC adhesion by promoting F-actin assembly, increasing cell spreading area, and inducing the osteogenic differentiation of the MSCs by the unique SF/GO nanofibrous matrix. To the best of our knowledge, it is the first report that the SF/GO substrates can induce the osteogenic differentiation of MSCs in the absence of osteogenic differentiation medium. Therefore, SF/GO composite materials would have a potential application in the field of bone tissue engineering.

Dataset Information

Activation of Human Natural Killer Cells by Graphene Oxide-Templated Antibody Nanoclusters.

Publications

Activation of Human Natural Killer Cells by Graphene Oxide-Templated Antibody Nanoclusters.

Similar Datasets

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