In vivo gold nanoparticle delivery of peptide vaccine induces anti-tumor immune response in prophylactic and therapeutic tumor models

Small. 2015 Mar 25;11(12):1453-1459. doi: 10.1002/smll.201402179. Epub 2014 Oct 29.

Abstract

Gold nanoparticles (AuNPs) are promising vehicles for cancer immunotherapy, with demonstrated efficacy in immune delivery and innate cell stimulation. Nevertheless, their potential has yet to be assessed in the in vivo application of peptide cancer vaccines. In this study, it is hypothesized that the immune distribution and adjuvant qualities of AuNPs could be leveraged to facilitate delivery of the ovalbumin (OVA) peptide antigen and the CpG adjuvant and enhance their therapeutic effect in a B16-OVA tumor model. AuNP delivery of OVA (AuNP-OVA) and of CpG (AuNP-CpG) enhanced the efficacy of both agents and induced strong antigen-specific responses. In addition, it is found that AuNP-OVA delivery alone, without CpG, is sufficient to promote significant antigen-specific responses, leading to subsequent anti-tumor activity and prolonged survival in both prophylactic and therapeutic in vivo tumor models. This enhanced therapeutic efficacy is likely due to the adjuvant effect of peptide coated AuNPs, as they induce inflammatory cytokine release when cultured with bone marrow dendritic cells. Overall, AuNP-mediated OVA peptide delivery can produce significant therapeutic benefits without the need of adjuvant, indicating that AuNPs are effective peptide vaccine carriers with the potential to permit the use of lower and safer adjuvant doses during vaccination.

Keywords: biodistribution; cancer; gold nanoparticles; immune system; immunotherapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cancer Vaccines / administration & dosage*
  • Cancer Vaccines / chemistry
  • Cell Line, Tumor
  • Diffusion
  • Gold / chemistry*
  • Humans
  • Metal Nanoparticles / chemistry
  • Mice
  • Nanocapsules / chemistry*
  • Nanocapsules / ultrastructure
  • Neoplasms, Experimental / immunology*
  • Neoplasms, Experimental / prevention & control*
  • Particle Size
  • Treatment Outcome
  • Vaccines, Subunit / administration & dosage*
  • Vaccines, Subunit / chemistry

Substances

  • Cancer Vaccines
  • Nanocapsules
  • Vaccines, Subunit
  • Gold