Phillips Classic Laser and Nanomedicine Laboratories, Winthrop P Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Nat Nanotechnol. 2009 Dec;4(12):855-60. doi: 10.1038/nnano.2009.333. Epub 2009 Nov 15.
The spread of cancer cells between organs, a process known as metastasis, is the cause of most cancer deaths. Detecting circulating tumour cells -- a common marker for the development of metastasis -- is difficult because ex vivo methods are not sensitive enough owing to limited blood sample volume and in vivo diagnosis is time-consuming as large volumes of blood must be analysed. Here, we show a way to magnetically capture circulating tumour cells in the bloodstream of mice followed by rapid photoacoustic detection. Magnetic nanoparticles, which were functionalized to target a receptor commonly found in breast cancer cells, bound and captured circulating tumour cells under a magnet. To improve detection sensitivity and specificity, gold-plated carbon nanotubes conjugated with folic acid were used as a second contrast agent for photoacoustic imaging. By integrating in vivo multiplex targeting, magnetic enrichment, signal amplification and multicolour recognition, our approach allows circulating tumour cells to be concentrated from a large volume of blood in the vessels of tumour-bearing mice, and this could have potential for the early diagnosis of cancer and the prevention of metastasis in humans.
癌细胞在器官之间的扩散,即转移过程,是大多数癌症死亡的原因。由于血液样本量有限,体外检测方法不够灵敏,而体内诊断由于必须分析大量血液而耗时较长,因此难以检测到循环肿瘤细胞——这是转移发展的常见标志物。在这里,我们展示了一种在小鼠血流中通过磁性捕获循环肿瘤细胞,然后快速光声检测的方法。经过功能化以靶向乳腺癌细胞中常见受体的磁性纳米颗粒在磁场下结合并捕获循环肿瘤细胞。为了提高检测的灵敏度和特异性,使用金- 碳纳米管与叶酸偶联作为光声成像的第二种对比剂。通过整合体内多重靶向、磁性富集、信号放大和多色识别,我们的方法可以从荷瘤小鼠血管中的大量血液中浓缩循环肿瘤细胞,这可能有助于癌症的早期诊断和人类转移的预防。