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In situ probing of cell–cell communications with surface-enhanced Raman scattering (SERS) nanoprobes and microfluidic networks for screening of immunotherapeutic drugs

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Abstract

Discovering novel drugs for cancer immunotherapy requires a robust in vitro drug screening platform that allows for straightforward probing of cell–cell communications. Here, we combined surface-enhanced Raman scattering (SERS) nanoprobes with microfluidic networks to monitor in situ the cancer–immune system intercellular communications. The microfluidic platform links up immune cells with cancer cells, where the cancer-cell secretions act as signaling mediators. First, gold@silver core–shell nanorods were employed to fabricate SERS immunoprobes for analysis of the signaling molecules. Multiple cancer secretions in a tumor microenvironment were quantitatively analyzed by a SERS-assisted three-dimensional (3D) barcode immunoassay with high sensitivity (1 ng/mL). Second, in an on-chip cell proliferation assay, multiple immunosuppressive proteins secreted by cancer cells were found to inhibit activation of immune cells, indicating that the platform simulates the physiological process of cancer–immune system communications. Furthermore, potential drug candidates were tested on this platform. A quantitative SERS immunoassay was performed to evaluate drug efficacy at regulating the secretion behavior of cancer cells and the activity of immune cells. This assay showed the suitability of this platform for in vitro drug screening. It is expected that the fully integrated and highly automated SERS-microfluidic platform will become a powerful analytical tool for probing intercellular communications and should accelerate the discovery and clinical validation of novel drugs.

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Acknowledgements

This research was supported by the National Natural Science of China (No. 61535003, 61177033 and 61275182), the Excellent Youth Foundation of Jiangsu Province (No. BK20140023), the National Basic Research Program of China (No. 2015CB352002), the Scientific Research Foundation of Graduate School of Southeast University (No. YBPY1507), the Science Foundation for the Excellent Youth Scholars of Southeast University and the Fundamental Research Funds for the Central Universities.

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Authors and Affiliations

  1. Advanced Photonics Center, School of Electronic Science and Engineering, Southeast University, Sipailou 2#, Nanjing, 210096, China

    Lei Wu, Zhuyuan Wang, Yizhi Zhang, Jiayuan Fei, Hui Chen, Shenfei Zong & Yiping Cui

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  1. Lei Wu
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  2. Zhuyuan Wang
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  3. Yizhi Zhang
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  4. Jiayuan Fei
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Correspondence to Zhuyuan Wang or Yiping Cui.

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12274_2016_1316_MOESM1_ESM.pdf

In situ probing of cell–cell communications with surfaceenhanced Raman scattering (SERS) nanoprobes and microfluidic networks for screening of immunotherapeutic drugs

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Wu, L., Wang, Z., Zhang, Y. et al. In situ probing of cell–cell communications with surface-enhanced Raman scattering (SERS) nanoprobes and microfluidic networks for screening of immunotherapeutic drugs. Nano Res. 10, 584–594 (2017). https://doi.org/10.1007/s12274-016-1316-2

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  • DOI: https://doi.org/10.1007/s12274-016-1316-2

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