Microfluidic chip enables single-cell measurement for multidrug resistance in triple-negative breast cancer cells

微流控芯片可对三阴性乳腺癌细胞的多药耐药性进行单细胞测量

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作者:Karan Parekh, Hamideh Sharifi Noghabi, Jose Alejandro Lopez, Paul Chi Hang Li

Aims

Triple-negative breast cancer patients are commonly treated with combination chemotherapy. Nonetheless, outcomes remain substandard with relapses being of a frequent occurrence. Among the several mechanisms that result in treatment failure, multidrug resistance, which is mediated by ATP-binding cassette proteins, is the most common. Regardless of the substantial studies conducted on the heterogeneity of cancer types, only a few assays can distinguish the variability in multidrug resistance activity between individual cells. We aim to develop a single-cell assay to study this.

Conclusion

The results display that drug accumulation in a single-cell greatly enhanced over its same-cell control because of inhibition by cyclosporine A. Furthermore, this experiment may provide a platform for future liquid biopsy studies to characterize the multidrug resistance activity at a single-cell level.

Methods

This experiment utilized a microfluidic chip to measure the drug accumulation in single breast cancer cells in order to understand the inhibition of drug efflux properties.

Results

Selection of single cells, loading of drugs, and fluorescence measurement for intracellular drug accumulation were all conducted on a microfluidic chip. As a result, measurements of the accumulation of chemotherapeutic drugs (e.g., daunorubicin and paclitaxel) in single cells in the presence and absence of cyclosporine A were conducted. Parameters such as initial drug accumulation, signal saturation time, and fold-increase of drug with and without the presence cyclosporine A were also tested.

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