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Graphene Oxides Decorated with Carnosine as an Adjuvant To Modulate Innate Immune and Improve Adaptive Immunity in Vivo

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† Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 518 Ziyue Road, Shanghai 200241, P. R. China
‡ Institute of Nano Biomedicine and Engineering, Key Laboratory of Thin Film and Microfabrication Technology of Ministry of Education, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, National Center for Translational Medicine, Collaborative Innovational Center for System Biology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P. R. China
§ Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, 48 Wenhui Road, Yangzhou 225009, P. R. China
∥ Department of Oncology, Shanghai Tongren Hospital, Shanghai Jiao Tong University School of Medicine, 1111 Xianxia Road, Shanghai 200336, P. R. China
⊥ Department of Oncology, Shanghai Renji Hospital, Shanghai Jiao Tong University School of Medicine, 160 Pujian Road, Shanghai 200127, P. R. China
*E-mail: [email protected]
*E-mail: [email protected]
Cite this: ACS Nano 2016, 10, 2, 2203–2213
Publication Date (Web):January 14, 2016
https://doi.org/10.1021/acsnano.5b06750
Copyright © 2016 American Chemical Society
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    Current studies have revealed the immune effects of graphene oxide (GO) and have utilized them as vaccine carriers and adjuvants. However, GO easily induces strong oxidative stress and inflammatory reaction at the site of injection. It is very necessary to develop an alternative adjuvant based on graphene oxide derivatives for improving immune responses and decreasing side effects. Carnosine (Car) is an outstanding and safe antioxidant. Herein, the feasibility and efficiency of ultrasmall graphene oxide decorated with carnosine as an alternative immune adjuvant were explored. OVA@GO-Car was prepared by simply mixing ovalbumin (OVA, a model antigen) with ultrasmall GO covalently modified with carnosine (GO-Car). We investigated the immunological properties of the GO-Car adjuvant in model mice. Results show that OVA@GO-Car can promote robust and durable OVA-specific antibody response, increase lymphocyte proliferation efficiency, and enhance CD4+ T and CD8+ T cell activation. The presence of Car in GO also probably contributes to enhancing the antigen-specific adaptive immune response through modulating the expression of some cytokines, including IL-6, CXCL1, CCL2, and CSF3. In addition, the safety of GO-Car as an adjuvant was evaluated comprehensively. No symptoms such as allergic response, inflammatory redness swelling, raised surface temperatures, physiological anomalies of blood, and remarkable weight changes were observed. Besides, after modification with carnosine, histological damages caused by GO-Car in lung, muscle, kidney, and spleen became weaken significantly. This study sufficiently suggest that GO-Car as a safe adjuvant can effectively enhance humoral and innate immune responses against antigens in vivo.

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    The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsnano.5b06750.

    • Stability of GO and GO-Car in physiological media, radiolabeling stability of 131I-GO and 131I-GO-Car, biodistribution of 131I-GO and 131I-GO-Car in mice, and the conjugation chemistry of GO with Car (PDF)

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