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

Romain Fevre1,2, Gaëtan Mary3, Nadia Vertti-Quintero2

  • 1Laboratoire d' Hydrodynamique (LadHyX), CNRS, EcolePolytechnique, InstitutPolytechnique de Paris, 91128 Palaiseau, France.

Iscience
|May 11, 2023
PubMed
Summary

This study demonstrates a microfluidic platform using anchored droplets for drug screening in Ewing sarcoma (EwS) spheroids. Sequential drug treatment with etoposide and cisplatin showed amplified synergistic effects, advancing precision medicine.

Keywords:
Biological science instrumentationCancerDrug delivery systemMolecular biology experimental approach

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Area of Science:

  • Biotechnology
  • Cancer Research
  • Drug Discovery

Background:

  • Microfluidic cell culturing, especially in 3D formats, holds promise for fundamental biology and precision cancer medicine.
  • Ewing sarcoma (EwS) is a rare bone cancer requiring effective therapeutic strategies.

Purpose of the Study:

  • To evaluate the response of EwS spheroids to drug combinations using a droplet-based microfluidic platform.
  • To assess the synergistic effects of etoposide and cisplatin in EwS cells.

Main Methods:

  • Culturing EwS A673 cell spheroids within 500 nL anchored droplets.
  • Merging cell-laden droplets with secondary droplets containing fluorescent-barcoded drugs.
  • Quantifying spheroid growth and viability using microscopy to determine IC50 values.
  • Evaluating synergistic drug combinations, including sequential treatments.

Main Results:

  • Microfluidic drug screening yielded IC50 values comparable to standard multiwell plate assays.
  • Sequential administration of etoposide followed by cisplatin 24 hours later demonstrated an amplified synergistic effect.
  • The droplet-based platform proved effective for evaluating drug combination efficacy.

Conclusions:

  • Droplet-based microfluidics provides a modular and efficient system for drug screening and combination evaluation.
  • Sequential drug treatment strategies can enhance therapeutic synergy in Ewing sarcoma.
  • This platform facilitates advancements in cancer precision medicine through improved drug response assessment.