title: Effective CpG DNA delivery using amphiphilic cycloamylose nanogels.
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.
authors.affiliation: Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan. akiyoshi@bio.polym.kyoto-u.ac.jp.
authors.forename: Y
authors.initials: Y
authors.lastname: Tahara
authors.forename: J
authors.initials: J
authors.lastname: Yasuoka
authors.forename: S
authors.initials: S
authors.lastname: Sawada
authors.forename: Y
authors.initials: Y
authors.lastname: Sasaki
authors.forename: K
authors.initials: K
authors.lastname: Akiyoshi
mesh_terms: D002412:Cations; D002784:Cholesterol / Q000737:chemistry*; D003505:Cyclodextrins / Q000737:chemistry* / Q000378:metabolism; D016207:Cytokines / Q000737:chemistry* / Q000378:metabolism; D004247:DNA / Q000008:administration & dosage / Q000737:chemistry*; D004337:Drug Carriers; D005021:Ethylamines / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry* / Q000378:metabolism; D008264:Macrophages / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism*; D000080385:Nanogels; D009838:Oligodeoxyribonucleotides; D054735:Phosphorothioate Oligonucleotides / Q000737:chemistry* / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry*
chemical_list: C408982:CPG-oligonucleotide; D002412:Cations; D003505:Cyclodextrins; D016207:Cytokines; D004337:Drug Carriers; D005021:Ethylamines; D008081:Liposomes; D000080385:Nanogels; D009838:Oligodeoxyribonucleotides; D054735:Phosphorothioate Oligonucleotides; C413692:polyethylene glycol polyethyleneimine nanogel; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D004247:DNA; D002784:Cholesterol