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

使用基于液滴的微流体技术对 3D 尤文氏肉瘤球体进行组合药物筛选

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

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.

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