Alum-functionalized graphene oxide nanocomplexes for effective anticancer vaccination

Acta Biomater. 2019 Jan 1:83:390-399. doi: 10.1016/j.actbio.2018.11.023. Epub 2018 Nov 15.

Abstract

Aluminum-based adjuvant (e.g., aluminum oxyhydroxide (AlO(OH), known as the commercial Alhydrogel® (Alum)) is the first adjuvant to be used in human vaccines. Although Alum shows a robust induction of antibody-mediated immunity, its weak stimulation of cell-mediated immunity makes it a questionable adjuvant for cancer immunotherapy. Herein, we described a novel formulation of Alum-based adjuvant by preparing AlO(OH)-modified graphene oxide (GO) nanosheets (GO-AlO(OH)), which, in addition to maintaining the induction of humoral immune response by AlO(OH), could further elicit the cellular immune response by GO. Similar to Alum, GO-AlO(OH) vaccine formulation could be constructed by the incorporation of antigen using a facile mixing/adsorption approach. Antigen-loaded GO-AlO(OH) nanocomplexes facilitated cellular uptake and cytosolic release of antigens and promoted DC maturation, thereby eliciting higher antigen-specific IgG titers, inducing robust CD4+ and CD8+ T lymphocyte response, and inhibiting tumor growth in vivo. Furthermore, by employing tumor cell lysate-based cancer vaccines, GO-AlO(OH) nanocomplexes led to significant inhibition of tumor growth and can be implemented as a personalized treatment strategy for cancer vaccine development. Overall, GO-AlO(OH) nanocomplexes described herein may serve as a facile and efficient approach for effective anticancer vaccination. STATEMENT OF SIGNIFICANCE: Herein, we described a novel formulation of aluminum-based adjuvant by preparing aluminum oxyhydroxide (AlO(OH)) (known as "Alum")-modified graphene oxide (GO) nanocomplexes (GO-AlO(OH)), which, in addition to maintaining the induction of humoral immune response by AlO(OH), could further elicit the cellular immune response by GO. GO-AlO(OH) nanocomplexes can be prepared easily and in large scale by a chemical precipitation method. Similar to "Alum," antigen-loaded GO-AlO(OH) vaccine formulation could be constructed by the incorporation of antigen using a facile mixing/adsorption approach. The very simple and reproductive preparation process of vaccines and the powerful ability to raise both humoral and cellular immune responses provide a novel approach for improving cancer immunotherapy efficacy.

Keywords: Adjuvant; Aluminum oxyhydroxide; Cancer immunotherapy; Graphene oxide; Vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic* / chemistry
  • Adjuvants, Immunologic* / pharmacology
  • Alum Compounds* / chemistry
  • Alum Compounds* / pharmacology
  • Animals
  • Antigens, Neoplasm* / chemistry
  • Antigens, Neoplasm* / immunology
  • Antigens, Neoplasm* / pharmacology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / pathology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / pathology
  • Cancer Vaccines
  • Dendritic Cells / immunology
  • Dendritic Cells / pathology
  • Graphite* / chemistry
  • Graphite* / pharmacology
  • Immunity, Cellular / drug effects
  • Melanoma, Experimental* / immunology
  • Melanoma, Experimental* / pathology
  • Melanoma, Experimental* / therapy
  • Mice
  • Nanostructures* / chemistry
  • Nanostructures* / therapeutic use

Substances

  • Adjuvants, Immunologic
  • Alum Compounds
  • Antigens, Neoplasm
  • Cancer Vaccines
  • graphene oxide
  • aluminum sulfate
  • Graphite