An important aspect of immunotherapy is the ability of dendritic cells (DCs) to prime T cell immunity, an approach that has yielded promising results in some early phase clinical trials. However, novel approaches are required to improve DC therapeutic efficacy by enhancing their uptake of, and activation by, disease relevant antigens. The carbon nano-material graphene oxide (GO) may provide a unique way to deliver antigen to innate immune cells and modify their ability to initiate effective adaptive immune responses. We have assessed whether GO of various lateral sizes affects DC activation and function in vitro and in vivo, including their ability to take up, process and present the well-defined model antigen ovalbumin (OVA). We have found that GO flakes are internalised by DCs, while having minimal effect on their viability, activation phenotype or cytokine production. Although adsorption of OVA protein to either small or large GO flakes promoted its uptake into DCs, large GO interfered with OVA processing. In terms of modulation of DC function, delivery of OVA via small GO flakes significantly enhanced DC ability to induce proliferation of OVA-specific CD4+ T cells, promoting granzyme B secretion in vitro. On the other hand, delivery of OVA via large GO flakes augmented DC ability to induce proliferation of OVA-specific CD8+ T cells, and their production of IFN-γ and granzyme B. Together, these data demonstrate the capacity of GO of different lateral dimensions to act as a promising delivery platform for DC modulation of distinct facets of the adaptive immune response, information that could be exploited for future development of targeted immunotherapies.
|Number of pages||18|
|Publication status||Published - 14 Nov 2022|
Bibliographical noteFunding Information:
This work was supported by the Engineering and Physical Sciences Research Council (EPSRC) under the 2D-Health Programme Grant [EP/P00119X/1]. The Bioimaging Facility Systems Microscopy Centre microscopes used in this study were purchased with grants from BBSRC, Wellcome and the University of Manchester Strategic Fund. Special thanks goes to Dave Spiller for his help with the microscopy. Thank you to Dr John Grainger for supplying us with OT-II × Rag-1 mice. The authors thank the staff of the Manchester Biological Services Facility for assistance. We would like to acknowledge Mr Alexander Fordham, NanoInflammation Team, Nanomedicine Lab, University of Manchester for running the endotoxin test of the materials. The Nanomedicine Group at ICN2 is partially supported by the CERCA programme, Generalitat de Catalunya, and the Severo Ochoa Centres of Excellence programme, funded by the Spanish Research Agency (AEI, grant no. SEV-2017-0706). −/−
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