title: Freezing-assisted intracellular drug delivery to multidrug resistant cancer cells.
abstract: 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.
authors.affiliation: Department of Mechanical and Aerospace Engineering, University of Texas at Arlington, Arlington, TX 76019, USA.
authors.forename: Ka Yaw
authors.initials: KY
authors.lastname: Teo
authors.forename: Bumsoo
authors.initials: B
authors.lastname: Han
mesh_terms: 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*
chemical_list: D000970:Antineoplastic Agents