TY - JOUR
T1 - Combinatorial drug screening on 3D Ewing sarcoma spheroids using droplet-based microfluidics
AU - Fevre, Romain
AU - Mary, Gaëtan
AU - Vertti-Quintero, Nadia
AU - Durand, Aude
AU - Tomasi, Raphaël F.X.
AU - Del Nery, Elaine
AU - Baroud, Charles N.
N1 - Publisher Copyright:
© 2023 The Authors
PY - 2023/5/19
Y1 - 2023/5/19
N2 - 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.
AB - 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.
KW - Biological science instrumentation
KW - Cancer
KW - Drug delivery system
KW - Molecular biology experimental approach
U2 - 10.1016/j.isci.2023.106651
DO - 10.1016/j.isci.2023.106651
M3 - Article
AN - SCOPUS:85153530490
SN - 2589-0042
VL - 26
JO - iScience
JF - iScience
IS - 5
M1 - 106651
ER -
