Tissue biodistribution and blood clearance rates of intravenously administered carbon nanotube radiotracers
Tissue biodistribution and blood clearance rates of intravenously administered carbon nanotube radiotracers
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DOI：
10.1073/pnas.0509009103
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发表时间：
2006-02-28
影响因子：
11.1
通讯作者：
Kostarelos, K
中科院分区：
文献类型：
--
作者：
Singh, R;Pantarotto, D;Kostarelos, K
碳纳米管（CNT）正在被大力开发用于生物医学应用，包括药物和基因递送。尽管所有可能的临床应用都将要求碳纳米管与生物环境具有相容性，但它们在体内的能力和局限性尚未得到探索。在这项工作中，水溶性单壁碳纳米管（SWNT）已用螯合分子二乙三胺五乙酸（DTPA）进行功能化，并标记上铟（In - 111）用于成像目的。对这些功能化的单壁碳纳米管（f - SWNT）进行静脉内（i.v.）给药，然后使用γ闪烁显像术进行放射性追踪，结果表明f - SWNT不会在任何网状内皮系统器官（肝脏或脾脏）中滞留，并且通过肾脏排泄途径从全身血液循环中迅速清除。观察到的f - SWNT的快速血液清除和半衰期（3小时）对碳纳米管的所有潜在临床用途都具有重要意义。此外，使用f - SWNT和功能化多壁碳纳米管进行的尿液排泄研究以及随后对尿液样本的电子显微镜分析显示，这两种类型的纳米管都是以完整的纳米管形式被排泄的。这项工作描述了静脉内给药的功能化碳纳米管的药代动力学参数，这些参数与各种治疗和诊断应用相关。
Carbon nanotubes (CNT) are intensively being developed for biomedical applications including drug and gene delivery. Although all possible clinical applications will require compatibility of CNT with the biological milieu, their in vivo capabilities and limitations have not yet been explored. In this work, water-soluble, single-walled CNT (SWNT) have been functionalized with the chelating molecule diethylentriaminepentaacetic (DTPA) and labeled with indium (In-111) for imaging purposes. Intravenous (i.v.) administration of these functionalized SWNT (f-SWNT) followed by radioactivity tracing using gamma scintigraphy indicated that f-SWNT are not retained in any of the reticuloendothelial system organs (liver or spleen) and are rapidly cleared from systemic blood circulation through the renal excretion route. The observed rapid blood clearance and half-life (3 h)of f-SWNT has major implications for all potential clinical uses of CNT. Moreover, urine excretion studies using both f-SWNT and functionalized multiwalled CNT followed by electron microscopy analysis of urine samples revealed that both types of nanotubes were excreted as intact nanotubes. This work describes the pharmacokinetic parameters of i.v. administered functionalized CNT relevant for various therapeutic and diagnostic applications.