Rapid Uptake of Gold Nanorods by Primary Human Blood Phagocytes and Immunomodulatory Effects of Surface Chemistry
Rapid Uptake of Gold Nanorods by Primary Human Blood Phagocytes and Immunomodulatory Effects of Surface Chemistry
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DOI：
10.1021/nn100262h
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发表时间：
2010-06-01
期刊：
影响因子：
17.1
通讯作者：
Groll, Juergen
中科院分区：
文献类型：
--
作者：
Bartneck, Matthias;Keul, Heidrun A.;Groll, Juergen
基于纳米颗粒的体内应用应该考虑到血液和组织中吞噬细胞的无处不在。我们使用纳米粒子库研究了最重要的人类初级白细胞的纳米粒子摄取能力，该纳米粒子库包括直径在15到50 nm之间的棒状和球形金纳米粒子以及各种表面化学物质。十六烷基三甲基溴化铵(CTAB)稳定的纳米粒在15分钟内被巨噬细胞大量内化，单核细胞也有少量内化。有趣的是，我们发现巨噬细胞对纳米棒的摄取比纳米球更有效。阻断实验和电子显微镜研究表明，巨噬细胞吞噬是主要的摄取机制。研究发现，聚环氧乙烷(PEO)接枝到纳米棒上可以显著延迟纳米棒的内化数小时。带有正负电荷端基的聚氧化乙烯包覆纳米颗粒的长期摄取几乎是相同的。颗粒表面化学在1天内强烈影响炎症相关基因的表达。此外，在纳米棒培养7天后，巨噬细胞的表型受到显著影响，这取决于表面化学。因此，在体内应用具有某些表面功能的纳米颗粒可能会导致颗粒聚集的炎症。然而，我们的数据也表明，纳米颗粒的化学修饰可能有助于免疫调节。
Nanopartide-based in vivo applications should consider the omnipresence of the phagocytes in the bloodstream and tissue. We have studied the nanoparticle uptake capacities of the most important human primary leukocyte populations using a nanoparticle library encompassing both rod-shaped and spherical gold nanoparticles with diameters between 15 and 50 nm and a variety of surface chemistries. Cetyltrimethyl-ammoniumbromide (CTAB)-stabilized nanoparticles were internalized rapidly within 15 min and in large amounts by macrophages and to a lower extent also by monocytes. Interestingly, we found that the uptake of nanorods by macrophages was more efficient than that of nanospheres. Blocking experiments and electron microscopic studies revealed macropinocytosis as the major uptake mechanism. Grafting of poly(ethylene oxide) (PEO) onto the nanorods was found to significantly delay their internalization for several hours. The long-term uptake of PEO-coated nanoparticles with positively or negatively charged end groups was almost identical. Particle surface chemistry strongly influenced the expression of inflammation-related genes within 1 day. Furthermore, the macrophage phenotype was significantly affected after 7 days of culture with nanorods depending on the surface chemistry. Thus, in vivo application of nanopartides with certain surface functionalities may lead to inflammation upon particle accumulation. However, our data also suggest that chemical modifications of nanoparticles may be useful for immunomodulation.