Institue of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.
Department of Urology, The First Affiliated Hospital of Xiamen University, Xiamen, 361003, Fujian, China.
J Nanobiotechnology. 2019 May 4;17(1):59. doi: 10.1186/s12951-019-0491-1.
Technology enabling the separation of rare circulating tumor cells (CTCs) provides the potential to enhance our knowledge of cancer metastasis and improve the care of cancer patients. Modern detection approaches commonly depend on tumor antigens or the physical size of CTCs. However, few studies report the detection of CTCs by the electrical differences between cancer cells and normal cells.
In this study, we report a procedure for capturing CTCs from blood samples using electrically charged superparamagnetic nanoparticles (NPs). We found that only positively charged NPs attached to cancer cells, while negatively charged NPs did not. The capture method with positively charged NPs offered a sensitivity of down to 4 CTCs in 1 mL blood samples and achieved a superior capture yield (> 70%) for a high number of CTCs in blood samples (10-10 cells/mL). Following an in vitro evaluation, S180-bearing mice were employed as an in vivo model to assess the specificity and sensitivity of the capture procedure. The number of CTCs in blood from tumor-bearing mice was significantly higher than that in blood from healthy controls (on average, 75.8 ± 16.4 vs. zero CTCs/100 μL of blood, p < 0.0001), suggesting the high sensitivity and specificity of our method.
Positively charged NPs combined with an in vivo tumor model demonstrated that CTCs can be distinguished and isolated from other blood cells based on their electrical properties.
使稀有循环肿瘤细胞（CTC）分离成为可能的技术提供了增强我们对癌症转移认识和改善癌症患者护理的潜力。现代检测方法通常依赖于肿瘤抗原或 CTC 的物理大小。然而，很少有研究报告通过癌细胞和正常细胞之间的电差异来检测 CTC。
在这项研究中，我们报告了一种使用带电超顺磁纳米粒子（NPs）从血液样本中捕获 CTC 的程序。我们发现只有带正电荷的 NPs 附着在癌细胞上，而带负电荷的 NPs 则没有。带正电荷的 NPs 的捕获方法对 1 mL 血液样本中的 4 个 CTCs 具有敏感性，并且对血液样本中的高数量 CTCs（10-10 个细胞/mL）实现了更高的捕获效率（>70%）。经过体外评估，我们使用携带 S180 的小鼠作为体内模型来评估捕获程序的特异性和敏感性。荷瘤小鼠血液中的 CTC 数量明显高于健康对照组（平均为 75.8±16.4 个/100 μL 血液，p<0.0001），表明我们的方法具有高灵敏度和特异性。
带正电荷的 NPs 与体内肿瘤模型相结合表明，可以根据其电学特性区分和分离 CTC 与其他血细胞。
