Freezing-assisted intracellular drug delivery to multidrug resistant cancer cells.
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 -20 degrees C, the intracellular uptake of calcein increased by 70.1% (n=5, P=0.0004). It further increased to 118% as NCI/ADR-RES cells were frozen/thawed to -40 degrees C (n=3, P=0.009). These results support the hypothesis, and possible mechanisms of F/T-enhanced intracellular drug delivery were proposed and discussed.
Teo
Ka Yaw
KY
Department of Mechanical and Aerospace Engineering, University of Texas at Arlington, Arlington, TX 76019, USA.
Han
Bumsoo
B
D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D016503:Drug Delivery Systems / Q000379:methods*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005615:Freezing; D006801:Humans; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*
D000970:Antineoplastic Agents