Theranostics 2018; 8(6):1624-1635. doi:10.7150/thno.23531

Research Paper

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

Qinqin Huang1,2,6, Fu-Bing Wang3, Chun-Hui Yuan3, Zhaobo He2, Lang Rao2, Bo Cai2, Bolei Chen5, Susu Jiang1,6, Zhiqiang Li1, Jincao Chen1, Wei Liu2, Feng Guo4, Zheng Ao4✉, Shi Chen1,6✉, Xing-Zhong Zhao2✉

1. Brain Center, Zhongnan Hospital, Wuhan University, Wuhan 430071, China.
2. Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan 430072, China.
3. Department of Laboratory Medicine, Zhongnan Hospital, Wuhan University, Wuhan 430071, China.
4. Department of Intelligent Systems Engineering, Indiana University, Bloomington, IN 47405, USA.
5. Institute for Interdisciplinary Research, Jianghan University, Wuhan 430056, China.
6. Key Laboratory of Combinatorial Biosynthesis and Drug Discovery of Ministry of Education, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China.

Abstract

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.

Keywords: circulating tumor cells, cell isolation, heterogeneous cells, precision medicine

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How to cite this article:
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. Gelatin Nanoparticle-Coated Silicon Beads for Density-Selective Capture and Release of Heterogeneous Circulating Tumor Cells with High Purity. Theranostics 2018; 8(6):1624-1635. doi:10.7150/thno.23531. Available from http://www.thno.org/v08p1624.htm