Effective CpG DNA delivery using amphiphilic cycloamylose nanogels

Biomater Sci. 2015 Feb;3(2):256-64. doi: 10.1039/c4bm00293h. Epub 2014 Oct 13.

Abstract

Unmethylated CpG oligodeoxynucleotides induce inflammatory immune responses through cytokine production and have attracted increasing attention as an immunostimulator. However, there remains a challenging issue of the use of 'native CpG DNA'. In the present study, we prepared cationic nanometer-sized gels (nanogels) consisting of cycloamylose modified with cholesterol and diethylaminoethane to form hydrophobic cross-linking points and to add positively charged groups, respectively. The cationic nanogels and native CpG DNA formed nanometer-sized complexes. Complexes of native CpG DNA with cationic nanogels delivered native CpG DNA to macrophage-like cells and induced cytokine production. In addition, complexes of negative control oligonucleotides with cationic nanogels did not induce cytokine production, and the induction of cytokines using complexes of phosphorothioate-modified CpG with cationic nanogels was lower than that of native CpG DNA. These results suggest that the complex of native CpG DNA with cationic nanogels is a promising strategy for nucleic acid adjuvants.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cations
  • Cholesterol / chemistry*
  • Cyclodextrins / chemistry*
  • Cyclodextrins / metabolism
  • Cytokines / chemistry*
  • Cytokines / metabolism
  • DNA / administration & dosage
  • DNA / chemistry*
  • Drug Carriers
  • Ethylamines / chemistry
  • Liposomes / chemistry*
  • Liposomes / metabolism
  • Macrophages / chemistry*
  • Macrophages / drug effects
  • Macrophages / metabolism*
  • Nanogels
  • Oligodeoxyribonucleotides
  • Phosphorothioate Oligonucleotides / chemistry*
  • Phosphorothioate Oligonucleotides / metabolism
  • Polyethylene Glycols / chemistry*
  • Polyethyleneimine / chemistry*

Substances

  • CPG-oligonucleotide
  • Cations
  • Cyclodextrins
  • Cytokines
  • Drug Carriers
  • Ethylamines
  • Liposomes
  • Nanogels
  • Oligodeoxyribonucleotides
  • Phosphorothioate Oligonucleotides
  • polyethylene glycol polyethyleneimine nanogel
  • Polyethylene Glycols
  • Polyethyleneimine
  • DNA
  • Cholesterol