Circulation and long-term fate of functionalized, biocompatible single-walled carbon nanotubes in mice probed by Raman spectroscopy
Circulation and long-term fate of functionalized, biocompatible single-walled carbon nanotubes in mice probed by Raman spectroscopy
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DOI：
10.1073/pnas.0707654105
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发表时间：
2008-02-05
影响因子：
11.1
通讯作者：
Dai, Hongjie
中科院分区：
文献类型：
--
作者：
Liu, Zhuang;Davis, Corrine;Dai, Hongjie
碳纳米管是生物系统中用于分子传递的有前景的新材料。目前尚不清楚纳米管在动物体内静脉注射后的长期命运，这对于这些材料的潜在临床应用至关重要。在此，利用单壁碳纳米管（SWNTs）固有的拉曼光谱特征，我们测量了静脉注射的单壁碳纳米管在血液中的循环情况，并在三个月的时间里在体外检测了小鼠各种器官和组织中的单壁碳纳米管。开发了通过支化聚乙二醇（PEG）链对单壁碳纳米管进行功能化的方法，从而实现了迄今为止最长可达1天的单壁碳纳米管血液循环，在网状内皮系统（RES）中的摄取相对较低，并且在大约2个月内从主要器官中几乎完全清除。拉曼光谱在小鼠的肠道、粪便、肾脏和膀胱中检测到了单壁碳纳米管，表明单壁碳纳米管通过胆汁和肾脏途径从小鼠体内排泄和清除。在尸检、组织学和血液化学测量中未观察到单壁碳纳米管对小鼠的毒性副作用。这些发现为碳纳米管未来的生物医学应用铺平了道路。
Carbon nanotubes are promising new materials for molecular delivery in biological systems. The long-term fate of nanotubes intravenously injected into animals in vivo is currently unknown, an issue critical to potential clinical applications of these materials. Here, using the intrinsic Raman spectroscopic signatures of single-walled carbon nanotubes (SWNTs), we measured the blood circulation of intravenously injected SWNTs and detect SWNTs in various organs and tissues of mice ex vivo over a period of three months. Functionalization of SWNTs by branched polyethyleneglycol (PEG) chains was developed, enabling thus far the longest SWNT blood circulation up to 1 day, relatively low uptake in the reticuloendothelial system (RES), and near-complete clearance from the main organs in approximate to 2 months. Raman spectroscopy detected SWNT in the intestine, feces, kidney, and bladder of mice, suggesting excretion and clearance of SWNTs from mice via the biliary and renal pathways. No toxic side effect of SWNTs to mice was observed in necropsy, histology, and blood chemistry measurements. These findings pave the way to future biomedical applications of carbon nanotubes.