Self-Assembled DNA Immunonanoflowers as Multivalent CpG Nanoagents

ACS Appl Mater Interfaces. 2015 Nov 4;7(43):24069-74. doi: 10.1021/acsami.5b06987. Epub 2015 Oct 22.

Abstract

Synthetic unmethylated cytosine-guanine (CpG) oligodeoxynucleotides are immunostimulatory motifs that have shown promise as vaccines or adjuvants for diseases such as cancers and infectious diseases. In the present work, novel immuno-nanoflowers (NFs), self-assembled from long DNA integrated with tandem CpG through rolling circle replication, were developed for efficient CpG delivery and protection from nuclease degradation. In a model of macrophage-like cells, the CpG NFs proved to be potent immunostimulators by triggering the proliferation of these immune cells, which, in turn, secreted immunostimulatory cytokines, including tumor necrosis factor α, interleukin-6, and interleukin-10. These results demonstrate the ability of CpG NFs to induce cancer cell apoptosis and necrosis.

Keywords: CpG ODNs; DNA; immunonanoflower; immunostimulation; nanoagent.

MeSH terms

  • Adjuvants, Immunologic / chemistry*
  • Amino Acid Motifs
  • Animals
  • Apoptosis
  • Biocompatible Materials / chemistry*
  • Cell Proliferation
  • CpG Islands*
  • DNA / chemistry
  • Fluorescein-5-isothiocyanate / chemistry
  • Interleukin-10 / metabolism
  • Interleukin-6 / metabolism
  • Macrophages / metabolism
  • Mice
  • Microscopy, Electron, Scanning
  • Nanoparticles / chemistry
  • Necrosis
  • Oligonucleotides / chemistry
  • RAW 264.7 Cells
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Adjuvants, Immunologic
  • Biocompatible Materials
  • IL10 protein, human
  • Interleukin-6
  • Oligonucleotides
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • DNA
  • Fluorescein-5-isothiocyanate