Alidori Simone, Thorek Daniel L J, Beattie Bradley J, Ulmert David, Almeida Bryan Aristega, Monette Sebastien, Scheinberg David A, McDevitt Michael R
Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
Departments of Radiology and Radiological Sciences, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America.
PLoS One. 2017 Aug 28;12(8):e0183902. doi: 10.1371/journal.pone.0183902. eCollection 2017.
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 [86Y]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 (t1/2 = 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.
纳米医学处于医学、生物工程和生物学的交叉点,通过创新和开发新药及设备,在改善健康方面具有巨大潜力。碳纳米管是一种有望转化为医学应用的纤维状纳米材料的例子。这类材料中的主要候选材料是铵功能化碳纳米管(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。在此,我们使用定量全身正电子发射断层扫描(PET)、药代动力学数据的房室模型、血清生物标志物和离体病理学研究,对非人类灵长类动物体内fCNT的分布、摄取和处理进行了多器官评估。肾脏和肝脏是在非人类灵长类动物中积累和排泄[86Y]fCNT的两个主要器官系统,如定量PET数据的房室模型分析所述,积累是细胞特异性的。一个串联的双房室模型解释了示踪剂标记的fCNT的肾脏处理过程;肝脏数据符合平行双房室模型。这些模型数据还显示,在3天内(t1/2 = 11.9小时),灵长类动物体内注射的活性物质有显著消除(>99.8%)。在非人类灵长类动物中获得的这些良好结果为fCNT在体内的命运提供了重要见解,并为复杂纳米药物的进一步工程设计考虑铺平道路,以帮助其后期开发和在人体中的临床应用。