Brain Center, Zhongnan Hospital, Wuhan University, Wuhan 430071, China.
Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan 430072, China.
Theranostics. 2018 Feb 7;8(6):1624-1635. doi: 10.7150/thno.23531. eCollection 2018.
Circulating tumor cells (CTCs) are a burgeoning topic in cancer biomarker discovery research with minimal invasive blood draws. CTCs can be used as potential biomarkers for disease prognosis, early cancer diagnosis and pharmacodynamics. However, the extremely low abundance of CTCs limits their clinical utility because of technical challenges such as the isolation and subsequent detailed molecular and functional characterization of rare CTCs from patient blood samples. In this study, we present a novel density gradient centrifugation method employing biodegradable gelatin nanoparticles coated on silicon beads for the isolation, release, and downstream analysis of CTCs from colorectal and breast cancer patients. Using clinical patient/spiked samples, we demonstrate that this method has significant CTC-capture efficiency (>80%) and purity (>85%), high CTC release efficiency (94%) and viability (92.5%). We also demonstrate the unparalleled robustness of our method in downstream CTC analyses such as the detection of PIK3CA mutations. The efficiency and versatility of the multifunctional density microbeads approach provides new opportunities for personalized cancer diagnostics and treatments.
循环肿瘤细胞（CTCs）是癌症生物标志物发现研究中的一个新兴课题，它通过微创采血来实现。CTCs 可以用作疾病预后、早期癌症诊断和药效学的潜在生物标志物。然而，由于技术挑战，如从患者血液样本中分离稀有 CTC 并对其进行详细的分子和功能特征分析，极低的 CTC 丰度限制了其临床应用。在这项研究中，我们提出了一种新颖的密度梯度离心方法，该方法使用涂有可生物降解明胶纳米粒子的硅珠来分离、释放和下游分析结直肠癌和乳腺癌患者的 CTC。使用临床患者/添加的样本，我们证明了该方法具有显著的 CTC 捕获效率（>80%）和纯度（>85%）、高 CTC 释放效率（94%）和活力（92.5%）。我们还证明了我们的方法在下游 CTC 分析中无与伦比的稳健性，如 PIK3CA 突变的检测。多功能密度微珠方法的效率和多功能性为个性化癌症诊断和治疗提供了新的机会。
