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使用基于微滴的微流控技术对三维尤因肉瘤球体进行组合药物筛选。

Combinatorial drug screening on 3D Ewing sarcoma spheroids using droplet-based microfluidics.

作者信息

Fevre Romain, Mary Gaëtan, Vertti-Quintero Nadia, Durand Aude, Tomasi Raphaël F-X, Del Nery Elaine, Baroud Charles N

机构信息

Laboratoire d' Hydrodynamique (LadHyX), CNRS, EcolePolytechnique, InstitutPolytechnique de Paris, 91128 Palaiseau, France.

Institut Pasteur, Université Paris Cité, Physical microfluidics and Bioengineering, 25-28 Rue du Dr. Roux, 75015 Paris, France.

出版信息

iScience. 2023 Apr 12;26(5):106651. doi: 10.1016/j.isci.2023.106651. eCollection 2023 May 19.

DOI:10.1016/j.isci.2023.106651
PMID:37168549
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10165258/
Abstract

Culturing and screening cells in microfluidics, particularly in three-dimensional formats, has the potential to impact diverse areas from fundamental biology to cancer precision medicine. Here, we use a platform based on anchored droplets for drug screening. The response of spheroids of Ewing sarcoma (EwS) A673 cells to simultaneous or sequential combinations of etoposide and cisplatin was evaluated. This was done by culturing spheroids of EwS cells inside 500 nL droplets then merging them with secondary droplets containing fluorescent-barcoded drugs at different concentrations. Differences in EwS spheroid growth and viability were measured by microscopy. After drug exposure such measurements enabled estimation of their IC50 values, which were in agreement with values obtained in standard multiwell plates. Then, synergistic drug combination was evaluated. Sequential combination treatment of EwS with etoposide applied 24 h before cisplatin resulted in amplified synergistic effect. As such, droplet-based microfluidics offers the modularity required for evaluation of drug combinations.

摘要

在微流控技术中培养和筛选细胞，尤其是在三维模式下，有可能影响从基础生物学到癌症精准医学等多个领域。在此，我们使用基于锚定液滴的平台进行药物筛选。评估了尤因肉瘤（EwS）A673细胞球体对依托泊苷和顺铂同时或序贯联合用药的反应。这是通过在500 nL液滴中培养EwS细胞球体，然后将它们与含有不同浓度荧光条形码药物的二级液滴合并来完成的。通过显微镜测量EwS球体生长和活力的差异。药物暴露后，此类测量能够估计其半数抑制浓度（IC50）值，这些值与在标准多孔板中获得的值一致。然后，评估了协同药物组合。在顺铂应用前24小时应用依托泊苷对EwS进行序贯联合治疗产生了增强的协同效应。因此，基于液滴的微流控技术提供了评估药物组合所需的模块性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1be/10165258/4f093a0a7ce6/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1be/10165258/86bc80a6a303/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1be/10165258/9d1042d0a83d/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1be/10165258/0f2a90ae7c5c/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1be/10165258/b8b6c868e121/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1be/10165258/69c6c49617b5/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1be/10165258/7e4837622a28/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1be/10165258/09c75b441afe/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1be/10165258/4f093a0a7ce6/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1be/10165258/86bc80a6a303/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1be/10165258/9d1042d0a83d/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1be/10165258/0f2a90ae7c5c/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1be/10165258/b8b6c868e121/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1be/10165258/69c6c49617b5/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1be/10165258/7e4837622a28/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1be/10165258/09c75b441afe/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1be/10165258/4f093a0a7ce6/gr7.jpg

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