Gelatin Nanoparticle-Coated Silicon Beads for Density-Selective Capture and Release of Heterogeneous Circulating Tumor Cells with High Purity.

Gelatin Nanoparticle-Coated Silicon Beads for Density-Selective Capture and Release of Heterogeneous Circulating Tumor Cells with High Purity.
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明胶纳米颗粒涂层硅珠,用于高纯度异质循环肿瘤细胞的密度选择性捕获和释放。

DOI:
10.7150/thno.23531
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发表时间:
2018
期刊:
影响因子:
12.4
通讯作者:
Zhao XZ
Zhao XZ
中科院分区:
医学1区
文献类型:
--
作者:
Huang Q;Wang FB;Yuan CH;He Z;Rao L;Cai B;Chen B;Jiang S;Li Z;Chen J;Liu W;Guo F;Ao Z;Chen S;Zhao XZ

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背景:循环肿瘤细胞(CTC)是微创抽血癌症生物标志物发现研究中的一个新兴课题。 CTC 可用作疾病预后、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,例如从患者血液样本中分离稀有 CTC 以及随后对其进行详细的分子和功能表征,CTC 的丰度极低,限制了其临床应用。方法:在本研究中,我们提出了一种新型密度梯度离心方法,采用涂在硅珠上的可生物降解明胶纳米颗粒,用于结直肠癌和乳腺癌患者的 CTC 的分离、释放和下游分析。结果:使用临床患者/加标样品,我们证明该方法具有显着的 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(例如 PIK3CA 突变检测)中无与伦比的稳健性。结论: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。
Background: 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. Methods: 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. Results: 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. Conclusion: The efficiency and versatility of the multifunctional density microbeads approach provides new opportunities for personalized cancer diagnostics and treatments.
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