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Assessment of multidrug resistance on cell coculture patterns using scanning electrochemical microscopy

Kuss, Sabine, Polcari, David, Geissler, Matthias, Brassard, Daniel, Mauzeroll, Janine
Proceedings of the National Academy of Sciences of the United States of America 2013 v.110 no.23 pp. 9249-9254
ABC transporters, adenocarcinoma, ammonia, coculture, drug therapy, drugs, electrochemistry, humans, metabolism, microscopy, multiple drug resistance, neoplasm cells, topography, uterine cervical neoplasms
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(NH ₃) 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.