Enhancement of anti-tumor effect of particulate vaccine delivery system by 'bacteriomimetic' CpG functionalization of poly-lactic-co-glycolic acid nanoparticles

Nanomedicine (Lond). 2015;10(6):915-29. doi: 10.2217/nnm.14.144.

Abstract

Aim: Low immunogenicity remains a major obstacle in realizing the full potential of cancer vaccines. In this study, we evaluated CpG-coated tumor antigen (Tag)-encapsulating 'bacteriomimetic' nanoparticles (CpG-nanoparticle [NP]-Tag NPs) as an approach to enhance anti-tumor immunity.

Materials & methods: CpG-NP-Tag NPs were synthesized, characterized for their physicochemical properties and tested in vivo.

Results: We found CpG predosing followed by intraperitoneal (IP) immunization with CpG-NP-Tag NPs significantly attenuated tumor growth in female BALB/c mice compared with respective controls. Histopathological and Immunofluorescence data revealed CpG-NP-Tag tumors had lower proliferation, higher apoptotic activity, greater CD4(+) and CD8(+) T cell infiltration as well as higher IFN-γ levels as compared with control groups.

Conclusion: Our findings suggest CpG-NP-Tag NPs can enhance anti-tumor effect of nanoparticulate tumor vaccination system.

Keywords: NP; antigen; breast cancer; immunotherapy; nanoparticle; vaccines.

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
  • Antigens, Neoplasm / chemistry*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / therapeutic use*
  • Apoptosis
  • CD4-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / cytology
  • Cancer Vaccines / immunology*
  • Cell Line, Tumor
  • Cell Proliferation
  • CpG Islands / genetics*
  • Drug Delivery Systems
  • Female
  • Interferon-gamma / metabolism
  • Ki-67 Antigen / metabolism
  • Lactic Acid / chemistry*
  • Luminescence
  • Mice
  • Mice, Inbred BALB C
  • Microscopy, Electron, Transmission
  • Microscopy, Fluorescence
  • Nanomedicine / methods
  • Nanoparticles / chemistry*
  • Neoplasms / immunology
  • Neoplasms / therapy
  • Particle Size
  • Polyglycolic Acid / chemistry*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Spectrometry, Fluorescence

Substances

  • Antigens, Neoplasm
  • Antineoplastic Agents
  • Cancer Vaccines
  • Ki-67 Antigen
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Interferon-gamma