Functionalized graphene oxide serves as a novel vaccine nano-adjuvant for robust stimulation of cellular immunity

Nanoscale. 2016 Feb 14;8(6):3785-95. doi: 10.1039/c5nr09208f. Epub 2016 Jan 27.

Abstract

Benefiting from their unique physicochemical properties, graphene derivatives have attracted great attention in biomedicine. In this study, we carefully engineered graphene oxide (GO) as a vaccine adjuvant for immunotherapy using urease B (Ure B) as the model antigen. Ure B is a specific antigen for Helicobacter pylori, which is a class I carcinogen for gastric cancer. Polyethylene glycol (PEG) and various types of polyethylenimine (PEI) were used as coating polymers. Compared with single-polymer modified GOs (GO-PEG and GO-PEI), certain dual-polymer modified GOs (GO-PEG-PEI) can act as a positive modulator to promote the maturation of dendritic cells (DCs) and enhance their cytokine secretion through the activation of multiple toll-like receptor (TLR) pathways while showing low toxicity. Moreover, this GO-PEG-PEI can serve as an antigen carrier to effectively shuttle antigens into DCs. These two advantages enable GO-PEG-PEI to serve as a novel vaccine adjuvant. In the subsequent in vivo experiments, compared with free Ure B and clinically used aluminum-adjuvant-based vaccine (Alum-Ure B), GO-PEG-PEI-Ure B induces stronger cellular immunity via intradermal administration, suggesting promising applications in cancer immunotherapy. Our work not only presents a novel, highly effective GO-based vaccine nano-adjuvant, but also highlights the critical roles of surface chemistry for the rational design of nano-adjuvants.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic* / chemistry
  • Adjuvants, Immunologic* / pharmacology
  • Animals
  • Antigens, Bacterial* / chemistry
  • Antigens, Bacterial* / pharmacology
  • Bacterial Proteins* / chemistry
  • Bacterial Proteins* / pharmacology
  • Bacterial Vaccines* / chemistry
  • Bacterial Vaccines* / pharmacology
  • Graphite* / chemistry
  • Graphite* / pharmacology
  • Helicobacter pylori / immunology*
  • Immunity, Cellular / drug effects*
  • Mice
  • Urease* / chemistry
  • Urease* / pharmacology

Substances

  • Adjuvants, Immunologic
  • Antigens, Bacterial
  • Bacterial Proteins
  • Bacterial Vaccines
  • Graphite
  • Urease