3 years ago

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

Carbohydrate-Functionalized rGO as an Effective Cancer Vaccine for Stimulating Antigen-Specific Cytotoxic T Cells and Inhibiting Tumor Growth
Ji Hoon Jeong, Pil J. Yoo, Youngjin Choi, Bong Geun Cha, Jaeyun Kim, Arjyabaran Sinha, Thanh Loc Nguyen
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.

Publisher URL: http://dx.doi.org/10.1021/acs.chemmater.7b02197

DOI: 10.1021/acs.chemmater.7b02197

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