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Published on: May 19, 2023
Characterisation of anticancer peptides at the single-cell level
L Armbrecht1, G Gabernet, F Kurth
1Department of Biosystems Science and Engineering, ETH Zurich, Switzerland. petra.dittrich@bsse.ethz.ch.
Abstract:
The development of efficacious anticancer therapeutics is difficult due to the heterogeneity of the cellular response to chemotherapy. Anticancer peptides (ACPs) are promising drug candidates that have been shown to be active against a range of cancer cells. However, few ACP studies focus on tumour single-cell heterogeneities. In order to address this need, we developed a microfluidic device and an imaging procedure that enable the capture, monitoring, and analysis of several hundred single cells for the study of drug response. MCF-7 human breast adenocarcinoma cells were captured in hydrodynamic traps and isolated in individual microchambers of less than 100 pL volume. With pneumatic valves, different sets of microchambers were actuated to expose the cells to various drugs. Here, the effect of three membranolytic ACPs - melittin, aurein 1.2 and aurein 2.2 - was investigated by monitoring the efflux of calcein from single MCF-7 cells. The loss of membrane integrity was observed with two different strategies that allow either focusing on one cell for mechanistic studies or parallel analysis of hundreds of individual cells. In general, the device is applicable to the analysis of the effect of various drugs on a large number of different cell types. The platform will enable us in the future to determine the origin of heterogeneous responses on pharmacological substances like ACPs within cell populations by combining it with other on-chip analytical methods.
Insights
This study introduces a microfluidic device to analyze anticancer peptide (ACP) drug responses in hundreds of single cancer cells, revealing cell-specific drug effects and overcoming treatment heterogeneity.
Area of Science:
- Biomedical Engineering
- Pharmacology
- Cancer Research
Background:
- Chemotherapy efficacy is limited by diverse cellular responses.
- Anticancer peptides (ACPs) show promise but their effects on tumor heterogeneity are understudied.
- Addressing single-cell heterogeneity is crucial for developing effective cancer therapeutics.
Purpose of the Study:
- To develop and validate a microfluidic platform for analyzing single-cell drug responses.
- To investigate the effects of membranolytic ACPs on MCF-7 breast cancer cells at the single-cell level.
- To provide a tool for studying drug response heterogeneity in cancer.
Main Methods:
- A microfluidic device with hydrodynamic traps and microchambers was designed for single-cell isolation.
- Pneumatic valves were used to expose individual cells to different anticancer peptides (melittin, aurein 1.2, aurein 2.2).
- Calcein dye efflux was monitored to assess membrane integrity and cell viability.
Main Results:
- The microfluidic platform successfully captured and isolated hundreds of single MCF-7 cells.
- The study monitored the membrane integrity loss in single cells upon exposure to three different ACPs.
- Two imaging strategies were employed for in-depth mechanistic studies and high-throughput parallel analysis.
Conclusions:
- The developed microfluidic device enables the analysis of drug effects on large populations of single cells.
- This platform is adaptable for various cell types and drug screening applications.
- Future integration with other on-chip methods will elucidate the origins of heterogeneous drug responses.
