Key Laboratory of Bioactive Materials for the Ministry of Education, College of Life Sciences, Nankai University, Tianjin, 300071, China.
J Nanobiotechnology. 2024 May 8;22(1):231. doi: 10.1186/s12951-024-02514-4.
Circulating tumor cells (CTCs) are considered as a useful biomarker for early cancer diagnosis, which play a crucial role in metastatic process. Unfortunately, the tumor heterogeneity and extremely rare occurrence rate of CTCs among billions of interfering leukocytes seriously hamper the sensitivity and purity of CTCs isolation.
To address these, we firstly used microfluidic chips to detect the broad-spectrum of triple target combination biomarkers in CTCs of 10 types of cancer patients, including EpCAM, EGFR and Her2. Then, we constructed hybrid engineered cell membrane-camouflaged magnetic nanoparticles (HE-CM-MNs) for efficient capture of heterogeneous CTCs with high-purity, which was enabled by inheriting the recognition ability of HE-CM for various CTCs and reducing homologous cell interaction with leukocytes. Compared with single E-CM-MNs, HE-CM-MNs showed a significant improvement in the capture efficiency for a cell mixture, with an efficiency of 90%. And the capture efficiency of HE-CM-MNs toward 12 subpopulations of tumor cells was ranged from 70 to 85%. Furthermore, by using HE-CM-MNs, we successfully isolated heterogeneous CTCs with high purity from clinical blood samples. Finally, the captured CTCs by HE-CM-MNs could be used for gene mutation analysis.
This study demonstrated the promising potential of HE-CM-MNs for heterogeneous CTCs detection and downstream analysis.
循环肿瘤细胞（CTCs）被认为是癌症早期诊断的有用生物标志物，在转移过程中起着至关重要的作用。不幸的是，肿瘤异质性和 CTC 在数十亿白细胞中极其罕见的发生率严重阻碍了 CTC 分离的灵敏度和纯度。
为了解决这些问题，我们首先使用微流控芯片检测了 10 种癌症患者 CTC 中广谱的三重靶标组合生物标志物，包括 EpCAM、EGFR 和 Her2。然后，我们构建了混合工程细胞膜伪装的磁性纳米颗粒（HE-CM-MNs），用于高效捕获具有高纯度的异质 CTC，这得益于 HE-CM 对各种 CTC 的识别能力的继承，以及减少了白细胞的同源细胞相互作用。与单 E-CM-MNs 相比，HE-CM-MNs 对细胞混合物的捕获效率显著提高，效率达到 90%。HE-CM-MNs 对 12 种肿瘤细胞亚群的捕获效率范围为 70%至 85%。此外，我们成功地使用 HE-CM-MNs 从临床血液样本中分离出具有高纯度的异质 CTC。最后，HE-CM-MNs 捕获的 CTC 可用于基因突变分析。
本研究表明 HE-CM-MNs 具有用于异质 CTC 检测和下游分析的巨大潜力。
