A polysaccharide carrier for immunostimulatory CpG DNAs to enhance cytokine secretion.

A polysaccharide carrier for immunostimulatory CpG DNAs to enhance cytokine secretion.
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DOI:
10.1021/ja031978
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发表时间:
2004-07
影响因子:
15
通讯作者:
M. Mizu;Kazuya Koumoto;T. Anada;Takahiro Matsumoto;Munenori Numata;S. Shinkai;T. Nagasaki;K. Sakurai
M. Mizu;Kazuya Koumoto;T. Anada;Takahiro Matsumoto;Munenori Numata;S. Shinkai;T. Nagasaki;K. Sakurai
中科院分区:
化学1区
文献类型:
--
作者:
M. Mizu;Kazuya Koumoto;T. Anada;Takahiro Matsumoto;Munenori Numata;S. Shinkai;T. Nagasaki;K. Sakurai

文献摘要

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β -(1—>3)-d-葡聚糖裂叶聚糖(SPG)与一些多核苷酸形成化学计量复合物。本文描述了我们利用SPG复合物将CpG DNA传递到核内体以增强细胞因子分泌的尝试。为了增加细胞摄取,我们在SPG侧链上引入精胺、精氨酸-甘氨酸-天冬氨酸三肽、辛精氨酸或胆固醇。化学修饰后的SPG基本没有细胞毒性。当CpG DNA复合物暴露于巨噬细胞时,观察到细胞因子分泌显著增强。比裸剂量增加5-10倍,比背景剂量增加100倍。这种性能预示着SPG可以成为CpG DNA的优良载体。
A beta-(1 --> 3)-d-glucan schizophyllan (SPG) forms a stoichiometric complex with some polynucleotides. This communication describes our attempt to apply the SPG complex to deliver CpG DNA to endosomes to enhance cytokine secretion. To increase cellular uptake, we introduced spermine, arginine-glycine-aspartic acid tripeptide, octaarginine, or cholesterol to the SPG side chain. The chemically modified SPG showed essentially no cytotoxicity. When CpG DNA complex made therefrom was exposed to macrophages, dramatic enhancement in the cytokine secretion was observed. It increased 5-10 times from the naked dose and 100 times from the background. This performance promises that SPG can be an excellent carrier for CpG DNA.