Peptides conjugated to gold nanoparticles induce macrophage activation
Peptides conjugated to gold nanoparticles induce macrophage activation
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DOI：
10.1016/j.molimm.2008.08.277
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发表时间：
2009-02-01
影响因子：
3.6
通讯作者：
Puntes, Victor
中科院分区：
文献类型：
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作者：
Bastus, Neus G.;Sanchez-Tillo, Ester;Puntes, Victor
巨噬细胞对致病生物起反应，也可以用人工纳米单位（由金纳米颗粒（Au NPs）组成）和肽包被激活。利用骨髓来源的巨噬细胞，我们发现这些细胞有能力识别与两种生物医学相关肽结合的Au NPs，即淀粉样蛋白生长抑制肽（AGIP）和甜箭肽（SAP），而它们不能识别单独的肽或NPs。巨噬细胞对这些缀合物的识别是由模式识别受体TLR-4介导的。因此，暴露于肽偶联的Au NPs时，可诱导tnf - α、IL-1 β和IL-6等促炎细胞因子以及一氧化氮合酶，并阻止巨噬细胞增殖。我们的实验系统中排除了脂多糖的污染。此外，巨噬细胞的激活似乎与肽的长度和极性无关。作为巨噬细胞活化的结果，偶联的Aut NPs被内化和加工。这些结果在佐剂领域开辟了一条新的途径，并说明了设计有效到达目标的NP偶联物的基本要求。(C) 2008 Elsevier Ltd版权所有。
Macrophages that react against pathogenic organisms can also be activated with artificial nanometric units consisting of gold nanoparticles (Au NPs) with a peptide coating. Using bone marrow-derived macrophages, here we show that these cells have the capacity to recognize Au NPs once conjugated to two biomedically relevant peptides, the amyloid growth inhibitory peptide (AGIP) and the sweet arrow peptide (SAP), while they do not recognize peptides or NPs alone. The recognition of these conjugates by macrophages is mediated by a pattern recognition receptor, the TLR-4. Consequently, pro-inflammatory cytokines such as TNF-alpha, IL-1 beta and IL-6, as well as nitric oxide synthase were induced and macrophage proliferation was stopped when exposed to the peptide-conjugated Au NPs. Contamination by lipopolysaccharide in our experimental system was excluded. Furthermore, macrophage activation appeared to be independent of peptide length and polarity. As a result of macrophage activation, conjugated Aut NPs were internalized and processed. These results open up a new avenue in the world of adjuvants and illustrate the basic requirements for the design of NP conjugates that efficiently reach their target. (C) 2008 Elsevier Ltd. All rights reserved.