Self-Assembling DNA Dendrimer for Effective Delivery of Immunostimulatory CpG DNA to Immune Cells

被引：58

作者：

Mohri, Kohta ^{[1
]}

Kusuki, Eri ^{[1
]}

Ohtsuki, Shozo ^{[1
]}

Takahashi, Natsuki ^{[1
]}

Endo, Masayuki ^{[2
]}

Hidaka, Kumi ^{[3
]}

Sugiyama, Hiroshi ^{[2
,3
]}

Takahashi, Yuki ^{[1
]}

Takakura, Yoshinobu ^{[1
]}

Nishikawa, Makiya ^{[1
]}

机构：

[1] Kyoto Univ, Dept Biopharmaceut & Drug Metab, Grad Sch Pharmaceut Sci, Sakyo Ku, Kyoto 6068501, Japan

[2] Kyoto Univ, Inst Integrated Cell Mat Sci WPI iCeMS, Sakyo Ku, Kyoto 6068501, Japan

[3] Kyoto Univ, Grad Sch Sci, Dept Chem, Sakyo Ku, Kyoto 6068502, Japan

来源：

BIOMACROMOLECULES | 2015年 / 16卷 / 04期

基金：

日本学术振兴会;

关键词：

BACTERIAL-DNA; MOTIFS; OLIGODEOXYNUCLEOTIDES; NANOSTRUCTURES; NANOCARRIERS; SYSTEMS; DESIGN;

D O I：

10.1021/bm501731f

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

DNA dendrimers consisting of several branched DNA units connected to each other using DNA ligase were quite effective for the delivery of immunostimulatory CpG DNA to immune cells. Therapeutic application of such DNA dendrimers, however, is hampered by the use of the ligase. Here, we report that self-assembling DNA dendrimers with high immunostimulatory potency can be prepared without DNA ligases. Annealing of DNA consisting of DNA units with elongated adhesive ends resulted in the formation of DNA dendrimers. Atomic force microscopy revealed that the several preparations of DNA dendrimers resulted in dendritic structures as designed. The cellular uptake of DNA dendrimers by mouse macrophage-like RAW264.7 cells and subsequent release of tumor necrosis factor-alpha were dependent on the structural complexity of the dendrimers. These results indicate that the ligation-free, self-assembling DNA dendrimers are a potent system for the delivery of immunostimulatory CpG DNA to immune cells.

引用

页码：1095 / 1101

页数：7

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