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.
Issue Section:
Technical Briefs
Keywords:
biomembrane transport,
biothermics,
cancer,
cellular biophysics,
drug delivery systems,
freezing,
melting,
molecular biophysics,
permeability,
proteins,
multidrug resistance,
drug delivery,
freezing,
quantitative fluorescence microscopy
Topics:
Cancer,
Drug delivery systems,
Drugs,
Freezing,
Proteins,
Fluorescence,
Membranes,
Cell membranes,
Microscopy
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