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Assessment of multidrug resistance on cell coculture patterns using scanning electrochemical microscopy
Sabine Kuss1, David Polcari, Matthias Geissler
1Department of Chemistry, Université du Québec à Montréal, Montreal, QC, Canada H2X 2J6.
Abstract:
The emergence of resistance to multiple unrelated chemotherapeutic drugs impedes the treatment of several cancers. Although the involvement of ATP-binding cassette transporters has long been known, there is no in situ method capable of tracking this transporter-related resistance at the single-cell level without interfering with the cell's environment or metabolism. Here, we demonstrate that scanning electrochemical microscopy (SECM) can quantitatively and noninvasively track multidrug resistance-related protein 1-dependent multidrug resistance in patterned adenocarcinoma cervical cancer cells. Nonresistant human cancer cells and their multidrug resistant variants are arranged in a side-by-side format using a stencil-based patterning scheme, allowing for precise positioning of target cells underneath the SECM sensor. SECM measurements of the patterned cells, performed with ferrocenemethanol and [Ru(NH3)6](3+) serving as electrochemical indicators, are used to establish a kinetic "map" of constant-height SECM scans, free of topography contributions. The concept underlying the work described herein may help evaluate the effectiveness of treatment administration strategies targeting reduced drug efflux.
Insights
Scanning electrochemical microscopy (SECM) offers a novel way to track cancer multidrug resistance at the single-cell level. This noninvasive method aids in evaluating treatment strategies by monitoring drug efflux.
Area of Science:
- Biomedical Engineering
- Analytical Chemistry
- Cancer Research
Background:
- Multidrug resistance (MDR) in cancer, often mediated by ATP-binding cassette transporters, hinders effective chemotherapy.
- Current methods for tracking MDR lack in situ, single-cell resolution without altering cellular conditions.
- There is a need for noninvasive techniques to monitor MDR mechanisms at the cellular level.
Purpose of the Study:
- To develop and validate a scanning electrochemical microscopy (SECM) method for tracking multidrug resistance protein 1 (MRP1)-dependent MDR.
- To quantitatively assess MDR in patterned cancer cells noninvasively.
- To establish a foundation for evaluating therapeutic strategies targeting drug efflux.
Main Methods:
- Utilized stencil-based patterning to arrange nonresistant and multidrug-resistant cancer cells side-by-side.
- Employed scanning electrochemical microscopy (SECM) with ferrocenemethanol and [Ru(NH3)6](3+) as electrochemical indicators.
- Generated constant-height SECM scans to create kinetic maps, minimizing topographical interference.
Main Results:
- Demonstrated SECM's capability to quantitatively and noninvasively track MRP1-dependent MDR in patterned adenocarcinoma cervical cancer cells.
- Successfully established kinetic maps of cellular activity, distinguishing resistant from nonresistant cells.
- Provided proof-of-concept for a single-cell, in situ method to monitor drug resistance.
Conclusions:
- SECM is a viable tool for noninvasive, single-cell analysis of transporter-mediated drug resistance.
- This approach can provide valuable insights into the efficacy of therapeutic interventions aimed at overcoming MDR.
- The developed method holds potential for optimizing cancer treatment strategies by monitoring drug efflux dynamics.
