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Issue 33, 2020
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Phenotype-related drug sensitivity analysis of single CTCs for medicine evaluation

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Abstract

Due to the heterogeneous and variable drug sensitivity of tumor cells, real-time monitoring of a patient's drug response is desirable for implementing personalized and dynamic therapy. Although considerable efforts have been directed at drug screening in living cells, performing repeated drug sensitivity analysis using patient-derived primary tumor cells at the single-cell level remains challenging. Here, we present an efficient approach to assess phenotype-related drug sensitivity at the single-cell level using patient-derived circulating tumor cells (CTCs) based on a drug sensitivity microfluidic chip (DS-Chip). The DS-Chip consists of a drug gradient generator and parallel cell traps, achieving continuous single CTC capture, drug gradient distributions, drug stimulation, fluorescent probe labeling and three-color fluorescence imaging. Based on the established DS-Chip, we investigated the drug sensitivity of single cells by simultaneously monitoring epithelial–mesenchymal transition (EMT) biomarkers and apoptosis in living cells, and verified the correlation between EMT gradients and drug sensitivity. Using the new approach, we further tested the optimal drug response dose in individual CTCs isolated from 5 cancer patients through fluorescence analysis of EMT and apoptosis. The DS-Chip allows noninvasive and real-time measurements of the drug sensitivity of a patient's tumor cells during therapy. This developed approach has practical significance and can effectively guide drug selection and therapeutic evaluation for personalized medicine.

Graphical abstract: Phenotype-related drug sensitivity analysis of single CTCs for medicine evaluation

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Supplementary files

Article information


Submitted
04 Nov 2019
Accepted
08 Aug 2020
First published
10 Aug 2020

This article is Open Access
All publication charges for this article have been paid for by the Royal Society of Chemistry

Chem. Sci., 2020,11, 8895-8900
Article type
Edge Article

Phenotype-related drug sensitivity analysis of single CTCs for medicine evaluation

H. Pei, M. Yu, D. Dong, Y. Wang, Q. Li, L. Li and B. Tang, Chem. Sci., 2020, 11, 8895
DOI: 10.1039/C9SC05566E

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