Effective CpG DNA delivery using amphiphilic cycloamylose nanogels

• Published in: Biomaterials science Vol. 3; no. 2; p. 256
• Main Authors: Tahara, Y, Yasuoka, J, Sawada, S, Sasaki, Y, Akiyoshi, K
• Format: Journal Article
• Language: English
• Published: England 01-01-2015
• Subjects: 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; Oligodeoxyribonucleotides; Phosphorothioate Oligonucleotides - chemistry; Phosphorothioate Oligonucleotides - metabolism; Polyethylene Glycols - chemistry; Polyethyleneimine - chemistry
• ISSN: 2047-4849
• DOI: 10.1039/c4bm00293h

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.