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使用碳纳米管作为“炸弹”试剂的癌细胞靶向与光声疗法。

Cancer-cell targeting and photoacoustic therapy using carbon nanotubes as "bomb" agents.

作者信息

Kang Bin, Yu Decai, Dai Yaodong, Chang Shuquan, Chen Da, Ding Yitao

机构信息

College of Material Science and Technology Nanjing University of Aeronautics and Astronautics Nanjing 210016, PR China.

出版信息

Small. 2009 Jun;5(11):1292-301. doi: 10.1002/smll.200801820.

DOI:10.1002/smll.200801820
PMID:19274646
Abstract

A unique approach using the large photoacoustic effect of single-walled carbon nanotubes (SWNTs) for targeting and selective destruction of cancer cells is demonstrated. SWNTs exhibit a large photoacoustic effect in suspension under the irradiation of a 1064-nm Q-switched millisecond pulsed laser and trigger a firecracker-like explosion at the nanoscale. By using such an explosion, a photoacoustic agent is developed by functionalizing the SWNTs with folate acid (FA) that can selectively bind to cancer cells overexpressing folate receptor on the surface of the cell membrane and kill them through SWNT explosion inside the cells under the excitation of millisecond pulsed laser. The uptake pathway of folate-conjugated SWNTs into cancer cells is investigated via fluorescence imaging and it is found that the FA-SWNTs can enter into cancer cells selectively with a high targeting capability of 17-28. Under the treatment of 1064-nm millisecond pulsed laser, 85% of cancer cells with SWNT uptake die within 20 s, while 90% of the normal cells remain alive due to the lack of SWNTs inside cells. Temperature changes during laser treatment are monitored and no temperature increases of more than +/- 3 degrees C are observed. With this approach, the laser power used for cancer killing is reduced 150-1500 times and the therapy efficiency is improved. The death mechanism of cancer cells caused by the photoacoustic explosion of SWNTs is also studied and discussed in detail. These discoveries provide a new way to use the photoacoustic properties of SWNTs for therapeutic applications.

摘要

展示了一种利用单壁碳纳米管(SWNTs)的大光声效应来靶向和选择性破坏癌细胞的独特方法。单壁碳纳米管在1064纳米调Q毫秒脉冲激光照射下在悬浮液中表现出大光声效应,并在纳米尺度引发类似鞭炮爆炸的现象。通过利用这种爆炸,通过用叶酸(FA)对单壁碳纳米管进行功能化来开发一种光声剂,叶酸可以选择性地与细胞膜表面过表达叶酸受体的癌细胞结合,并在毫秒脉冲激光激发下通过细胞内单壁碳纳米管爆炸杀死癌细胞。通过荧光成像研究了叶酸偶联的单壁碳纳米管进入癌细胞的摄取途径,发现叶酸 - 单壁碳纳米管可以选择性地进入癌细胞,靶向能力高达17 - 28。在1064纳米毫秒脉冲激光处理下,摄取单壁碳纳米管的85%癌细胞在20秒内死亡,而90%的正常细胞由于细胞内缺乏单壁碳纳米管而存活。监测激光治疗期间的温度变化,未观察到温度升高超过±3摄氏度。采用这种方法,用于杀死癌细胞的激光功率降低了150 - 1500倍,治疗效率得到提高。还详细研究和讨论了单壁碳纳米管光声爆炸导致癌细胞的死亡机制。这些发现为利用单壁碳纳米管的光声特性进行治疗应用提供了一种新方法。

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Small. 2009 Jun;5(11):1292-301. doi: 10.1002/smll.200801820.
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