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Carbohydrate-Functionalized rGO as an Effective Cancer Vaccine for Stimulating Antigen-Specific Cytotoxic T Cells and Inhibiting Tumor Growth

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† § ∥ †School of Chemical Engineering, ‡School of Pharmacy, §Department of Health Sciences and Technology, Samsung Advanced Institute for Health Science & Technology (SAIHST), ∥Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University (SKKU), Suwon 16419, Republic of Korea
*E-mail: [email protected]; Tel.: +82-31-290-7252; Fax: +82-31-290-7272.
Cite this: Chem. Mater. 2017, 29, 16, 6883–6892
Publication Date (Web):July 28, 2017
https://doi.org/10.1021/acs.chemmater.7b02197
Copyright © 2017 American Chemical Society
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    Abstract

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    Efficient delivery of antigens to dendritic cells (DCs), potent antigen-presenting cells, and subsequent antigen presentation to initiate the production of activated cytotoxic T cells are vital parameters that determine the success of cancer immunotherapy. Here, we report dextran-functionalized reduced graphene oxide (rGO-dextran) as an antigen delivery carrier for cancer immunotherapy. We synthesized dextran-functionalized rGO, where the dextran component facilitated good colloidal stability by exposing hydroxyl groups on the surface of reduced graphene oxide (rGO) and also enhanced cellular uptake via interaction with carbohydrate receptors present on DCs. High surface area and intrinsic hydrophobic surface of rGO facilitated high loading of the model antigen, ovalbumin (OVA). We found that rGO-dextran efficiently delivered OVA to DCs and enhanced the antigen presentation via major histocompatibility complex class I (MHC-I). In addition, the release of inflammatory cytokines, IL-12 and TNF-α, for DCs incubated with OVA-loaded rGO-dextran was remarkably higher than that for those incubated with soluble OVA. We also demonstrated that OVA-loaded rGO-dextran induced production of antigen-specific cytotoxic T cells in vivo and significantly inhibited tumor growth. Therefore, the proposed rGO-dextran could be a potent candidate for cancer vaccine and other immunotherapy.

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    The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.chemmater.7b02197.

    • Characterization of OVA-FITC loading, release profile of OVA-FITC from rGO-dextran, effect of rGO-dextran-40/rGO-dextran-6 on activation of BMDCs, effect of dextran OVA mixture and OVA@rGO on the maturation of BMDCs, and in vivo imaging of lymph node after subcutaneous injection of R6g@rGO-dextran in mice (PDF)

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