The efficacy of chemotherapy is significantly impaired by the multidrug resistance (MDR) of cancer cells. The mechanism of MDR is associated with the overexpression of certain adenosine triphosphate-binding cassette protein transporters in plasma membranes, which actively pump out cytotoxic drugs from the intracellular space. In this study, we tested a hypothesis that freezing and thawing (F/T) may enhance intracellular drug delivery to MDR cancer cells via F/T-induced denaturation of MDR-associated proteins and/or membrane permeabilization. After a human MDR cancer cell line (NCI/ADR-RES) was exposed to several F/T conditions, its cellular drug uptake was quantified by a fluorescent calcein assay using calcein as a model drug. After F/T to , the intracellular uptake of calcein increased by 70.1% (, ). It further increased to 118% as NCI/ADR-RES cells were frozen/thawed to (, ). These results support the hypothesis, and possible mechanisms of F/T-enhanced intracellular drug delivery were proposed and discussed.
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July 2009
Technical Briefs
Freezing-Assisted Intracellular Drug Delivery to Multidrug Resistant Cancer Cells
Ka Yaw Teo,
Ka Yaw Teo
Department of Mechanical and Aerospace Engineering,
University of Texas at Arlington
, Arlington, TX 76019
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Bumsoo Han
Bumsoo Han
Assistant Professor
Department of Mechanical and Aerospace Engineering,
e-mail: bhan@uta.edu
University of Texas at Arlington
, Arlington, TX 76019
Search for other works by this author on:
Ka Yaw Teo
Department of Mechanical and Aerospace Engineering,
University of Texas at Arlington
, Arlington, TX 76019
Bumsoo Han
Assistant Professor
Department of Mechanical and Aerospace Engineering,
University of Texas at Arlington
, Arlington, TX 76019e-mail: bhan@uta.edu
J Biomech Eng. Jul 2009, 131(7): 074513 (4 pages)
Published Online: June 29, 2009
Article history
Received:
September 1, 2008
Revised:
April 27, 2009
Published:
June 29, 2009
Citation
Teo, K. Y., and Han, B. (June 29, 2009). "Freezing-Assisted Intracellular Drug Delivery to Multidrug Resistant Cancer Cells." ASME. J Biomech Eng. July 2009; 131(7): 074513. https://doi.org/10.1115/1.3153325
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