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Microfluidic device for the analysis of MDR cancerous cell-derived exosomes’ response to nanotherapy

  • Ruogu Qi
  • Guixian Zhu
  • Yu Wang
  • Suhong Wu
  • Shengliang Li
  • Dechen Zhang
  • Yang Bu
  • Gauri Bhave
  • Ruixuan Han
  • Xuewu LiuEmail author
Article
  • 324 Downloads
Part of the following topical collections:
  1. Biomedical Micro-Nanotechnologies toward Translation

Abstract

Exosomes are membrane-enclosed extracellular vesicles which have been indicated as important biomarkers of cancerous cell functionality, such as multiple drug resistance (MDR). Nanoparticles based chemotherapy is a promising strategy to overcome MDR by interfering the production and composition of exosomes. Therefore, tumor-derived exosomes post-treatment by nanotherapy are implied to play critical roles of biomarkers on cancer MDR analysis. However, the efficient isolation of such exosomes from extracellular environment for their therapeutic response analysis remains challenging. In this study, we presented a microfluidic device featured exosome specific anti-CD63 immobilized ciliated micropillars, which were capable to isolate cancer-derived exosomes from cell culture medium. The captured exosomes can be recovered intact by dissolving the cilia on the micropillars using PBS soaking. Owing to the immobilized antibody in the microfluidic device, nearly 70% of exosome from the biofluid could be isolated. So the secreted exosomes of the MDR and ordinary human breast cancer cells pre-treated by free drug or nanotherapy could be isolated with high purity. The drug contents of the isolated exosomes were measured to analysis of the exosomal pathway response of MDR cells to different chemotherapeutic formulations. Such analyses and further definition of the biomarkers of these exosomes could benefit the future investigations of accurately and reliably determine design principle, functional activity, and mechanisms of nanotherapy for MDR overcoming.

Keywords

Exosome Microfluidic device Isolation Nanoparticles therapy Multiple drug resistance 

Notes

Acknowledgements

The authors would like to thank Dr. Jianhua Gu of the HMRI Microscopy-SEM/AFM core on AFM imaging. The authors acknowledge financial support from the following sources: NIH 1R21CA190024-01, 1R01GM127558-01, DOD W81XWH-17-1-0389 and Houston Methodist Research Institute.

Supplementary material

10544_2019_381_MOESM1_ESM.pdf (524 kb)
ESM 1 (PDF 340 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of NanomedicineHouston Methodist Research InstituteHoustonUSA

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