National Institute of Advanced Industrial Science and Technology, Nanotube Research Center, 5-2, 1-1-1 Higashi, Tsukuba 305-8565, Japan.
Biomaterials. 2012 Mar;33(9):2762-9. doi: 10.1016/j.biomaterials.2011.12.023. Epub 2011 Dec 30.
Cellular responses to graphene-based, nanometer-sized materials, such as carbon nanotubes and single-walled carbon nanohorns (SWNHs), have previously been studied at low-uptake levels. Here, by exploiting the availability of large quantities of SWNHs, cytotoxicity and the immunological responses induced by the abundant uptake of these structures were studied in RAW 264.7 murine macrophages. As much as half the cell interior was pigmented black by SWNHs, which were preferentially localized to lysosomes. High-uptake was shown to destabilize lysosomal membranes and generate reactive oxygen species that resulted in apoptotic, as well as necrotic, cell death. Despite these dramatic responses, only low levels of cytokines were released. The results will be interesting for future studies of the nanocarbon toxicity mechanisms and for medical applications of nanocarbons, especially those relying on lysosomes as target organelles for drug delivery or imaging.
先前已经研究过基于石墨烯的纳米级材料(如碳纳米管和单壁碳纳米角)对细胞的反应,其摄取水平较低。在这里,通过利用大量的单壁碳纳米角,研究了 RAW 264.7 鼠巨噬细胞对这些结构大量摄取所引起的细胞毒性和免疫反应。单壁碳纳米角使多达一半的细胞内部被染成黑色,这些角优先定位于溶酶体。高摄取量被证明会破坏溶酶体膜并产生活性氧,导致细胞凋亡和坏死。尽管有这些剧烈的反应,但只释放出低水平的细胞因子。这些结果对于未来研究纳米碳毒性机制以及纳米碳在医学上的应用(特别是那些依赖溶酶体作为药物输送或成像的靶向细胞器的应用)将非常有趣。