Immunostimulatory properties of CpG-oligonucleotides are enhanced by the use of protamine nanoparticles
Immunostimulatory properties of CpG-oligonucleotides are enhanced by the use of protamine nanoparticles
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DOI：
10.1089/oli.2006.16.313
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发表时间：
2006-01-01
期刊：
影响因子：
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通讯作者：
Hartmann, Gunther
中科院分区：
文献类型：
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作者：
Kerkmann, Miren;Lochmann, Dirk;Hartmann, Gunther
本研究旨在探讨可生物降解的鱼精蛋白纳米粒（profectamine nanoparticles，profectamine）能否增强CpG寡核苷酸（CpG-ODN）的免疫刺激作用。我们用光子相关光谱和透射电子显微镜分析了含有CpG-ODN的鱼精蛋白纳米颗粒的尺寸、表面电荷和形态。研究了这些纳米颗粒对B细胞、浆细胞样树突状细胞（PDC）、外周血单个核细胞和全血的免疫刺激作用。检查了细胞因子的产生、细胞在表面分子上调和纳米颗粒摄取方面的活化。我们发现，使用鱼精蛋白纳米颗粒显著增加了（20倍）CpG-ODN介导的PDC的干扰素（IFN）-α产生。PDC中的ODN摄取仅略微增强。CpG-ODN介导的IP-10在全血中的生产强烈增强通过使用纳米颗粒。除了CpG-ODN诱导的B细胞中白细胞介素（IL）-6产生略有增加外，其他参数如CpG介导的B细胞和PDC的活化以及PDC的肿瘤坏死因子（TNF）-α产生基本保持不变。使用对照ODN表明鱼精蛋白纳米颗粒本身没有免疫刺激特性。这些结果强烈支持使用颗粒递送系统如生物可降解的鱼精蛋白纳米颗粒用于开发基于CpG-ODN的治疗剂。
The aim of this paper was to investigate if the immunostimulatory effects of CpG-oligonucleotides (CpG-ODN) can be enhanced by the use of biodegradable protamine nanoparticles (proticles). We analyzed size, surface charge, and morphology of protamine nanoparticles containing CpG-ODN with photon correlation spectroscopy and transmission electron microscopy. Immunostimulatory effects of these nanoparticles on B cells, plasmacytoid dendritic cells (PDC), peripheral blood mononuclear cells, and whole blood were studied. Cytokine production, activation of the cells in terms of upregulation of surface molecules and uptake of nanoparticles were examined. We found that the use of protamine nanoparticles significantly increased (20-fold) CpG-ODN mediated interferon (IFN)-alpha production of PDC. ODN uptake in PDC was only marginally enhanced. CpG-ODN mediated IP-10 production in whole blood was strongly enhanced by the use of nanoparticles. Apart from a slight increase in CpG-ODN-induced interleukin (IL)-6 production in B cells, other parameters like the CpG-mediated activation of B cells and PDC as well as tumor necrosis factor (TNF)-alpha production of PDC remained largely unchanged. The use of control ODN indicated that the protamine nanoparticles themselves have no immunostimulatory properties. These results strongly support the use of particulate delivery systems like biodegradable protamine nanoparticles for the development of CpG-ODN-based therapeutics.