Luna Innovations Inc., Nanoworks Division, Danville, Virginia 24541, USA.
Nanomedicine. 2010 Aug;6(4):575-82. doi: 10.1016/j.nano.2010.01.008. Epub 2010 Feb 4.
Fullerenes are carbon cages of variable size that can be derivatized with various side chain moieties resulting in compounds that are being developed into nanomedicines. Although fullerene use in several preclinical in vitro and in vivo models of disease has demonstrated their potential as diagnostic and therapeutic agents, little is known about how they enter cells, what organelles they target, and the time course for their cellular deposition. Fullerenes (C(70)) that have already been shown to be potent inhibitors of mast cell (MC)-mediated allergic inflammation were conjugated with Texas red (TR) and used in conjunction with confocal microscopy to determine mechanisms of uptake, the organelle localization, and the duration they can be detected in situ. We show that C(70)-TR are nonspecifically endocytosed into MCs, where they are shuttled throughout the cytoplasm, lysosomes, mitochondria, and into endoplasmic reticulum at different times. No nuclear or secretory granule localization was observed. The C(70)-TR remained detectable within cells at 1 week. These studies show that MCs endocytose fullerenes, where they are shuttled to organelles involved with calcium and reactive oxygen species production, which may explain their efficacy as cellular inhibitors. From the clinical editor: Fullerenes are carbon cages of variable size that have already been shown to be potent inhibitors of mast cell (MC)-mediated allergic inflammation. These were conjugated with Texas red (TR) and used in conjunction with confocal microscopy to determine mechanisms of uptake, the organelle localization, and duration, demonstrating that MCs endocytose fullerenes, which are shuttled to organelles involved with calcium and reactive oxygen species production. This intracellular trafficking may explain the efficacy of fullerenes as cellular inhibitors.
富勒烯是具有可变大小的碳笼，可用各种侧链基团衍生化，得到正在开发为纳米药物的化合物。尽管富勒烯在几种疾病的临床前体外和体内模型中已显示出作为诊断和治疗剂的潜力，但对于它们如何进入细胞、靶向哪些细胞器以及其细胞沉积的时间过程知之甚少。已经显示出富勒烯（C（70））是肥大细胞（MC）介导的过敏炎症的有效抑制剂，它们与 Texas Red（TR）缀合，并与共聚焦显微镜一起使用，以确定摄取机制、细胞器定位以及它们在原位可检测的持续时间。我们表明，C（70）-TR 是非特异性地内吞到 MC 中，在 MC 中它们被穿梭到细胞质、溶酶体、线粒体和内质网中，在不同时间到达这些细胞器。未观察到核或分泌颗粒定位。在 1 周内，C（70）-TR 仍可在细胞内检测到。这些研究表明，MC 内吞富勒烯，它们被运送到涉及钙和活性氧物质产生的细胞器，这可能解释了它们作为细胞抑制剂的功效。从临床编辑的角度来看：富勒烯是具有可变大小的碳笼，已被证明是肥大细胞（MC）介导的过敏炎症的有效抑制剂。这些与 Texas Red（TR）缀合，并与共聚焦显微镜一起使用，以确定摄取机制、细胞器定位和持续时间，表明 MC 内吞富勒烯，富勒烯被运送到涉及钙和活性氧物质产生的细胞器。这种细胞内运输可能解释了富勒烯作为细胞抑制剂的功效。
