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

Author:
Kuss, Sabine, Polcari, David, Geissler, Matthias, Brassard, Daniel, Mauzeroll, Janine
Source:
Proceedings of the National Academy of Sciences of the United States of America 2013 v.110 no.23 pp. 9249-9254
ISSN:
0027-8424
Subject:
ABC transporters, adenocarcinoma, ammonia, coculture, drug therapy, drugs, electrochemistry, humans, metabolism, microscopy, multiple drug resistance, neoplasm cells, topography, uterine cervical neoplasms
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(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.
Agid:
1736911