Carbon nanotubes exhibit fibrillar pharmacology in primates
Carbon nanotubes exhibit fibrillar pharmacology in primates
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DOI：
10.1371/journal.pone.0183902
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发表时间：
2017-08-28
期刊：
影响因子：
3.7
通讯作者：
McDevitt, Michael R.
中科院分区：
文献类型：
--
作者：
Alidori, Simone;Thorek, Daniel L. J.;McDevitt, Michael R.
纳米医学是医学、生物工程和生物学的结合体，具有通过创新和开发新药和设备来改善健康的巨大潜力。碳纳米管是纤维状纳米材料有望转化为医疗实践的一个例子。这类材料的主要候选材料是氨功能化碳纳米管（fCNT），它在体内表现出意想不到的药理行为，具有重要的生物技术应用。在这里，我们通过定量全身正电子发射断层扫描（PET）、药代动力学数据的室室建模、血清生物标志物和离体病理研究，对非人灵长类动物fCNT的分布、摄取和加工进行了多器官评估。肾脏和肝脏是非人灵长类动物中积累和排泄fCNT的两个主要器官系统[Y-86]，并且通过定量PET数据的区室建模分析，积累是细胞特异性的。一个连续的双室模型解释了示踪剂标记的fCNT的肾脏处理；肝脏数据符合平行双室模型。这些建模数据还显示，在3天（t(1/2) = 11.9小时）内，灵长类动物的注射活性（>99.8%）显著消除。这些在非人类灵长类动物中的有利结果为fCNT在体内的命运提供了重要的见解，并为进一步考虑复杂纳米药物的工程设计铺平了道路，以帮助人类的后期开发和临床应用。
Nanomedicine rests at the nexus of medicine, bioengineering, and biology with great potential for improving health through innovation and development of new drugs and devices. Carbon nanotubes are an example of a fibrillar nanomaterial poised to translate into medical practice. The leading candidate material in this class is ammonium-functionalized carbon nanotubes (fCNT) that exhibits unexpected pharmacological behavior in vivo with important biotechnology applications. Here, we provide a multi-organ evaluation of the distribution, uptake and processing of fCNT in nonhuman primates using quantitative whole body positron emission tomography (PET), compartmental modeling of pharmacokinetic data, serum biomarkers and ex vivo pathology investigation. Kidney and liver are the two major organ systems that accumulate and excrete [Y-86] fCNT in nonhuman primates and accumulation is cell specific as described by compartmental modeling analyses of the quantitative PET data. A serial two-compartment model explains renal processing of tracer-labeled fCNT; hepatic data fits a parallel two-compartment model. These modeling data also reveal significant elimination of the injected activity (>99.8%) from the primate within 3 days (t(1/2) = 11.9 hours). These favorable results in nonhuman primates provide important insight to the fate of fCNT in vivo and pave the way to further engineering design considerations for sophisticated nanomedicines to aid late stage development and clinical use in man.