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Freezing-assisted intracellular drug delivery to multidrug resistant cancer cells

Ka Yaw Teo1, Bumsoo Han

  • 1Department of Mechanical and Aerospace Engineering, University of Texas at Arlington, Arlington, TX 76019, USA.

Journal of Biomechanical Engineering
|July 31, 2009
PubMed

Insights

Freezing and thawing (F/T) can overcome multidrug resistance (MDR) in cancer cells. This method enhances intracellular drug delivery by increasing drug uptake in MDR cancer cells.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Oncology

Background:

  • Multidrug resistance (MDR) in cancer cells significantly reduces chemotherapy efficacy.
  • MDR is often mediated by ATP-binding cassette transporters that efflux drugs.
  • Targeting MDR is crucial for improving cancer treatment outcomes.

Purpose of the Study:

  • To investigate if freezing and thawing (F/T) can enhance intracellular drug delivery to multidrug-resistant (MDR) cancer cells.
  • To test the hypothesis that F/T induces protein denaturation or membrane permeabilization, improving drug uptake.
  • To quantify the effect of F/T on drug delivery in a human MDR cancer cell line.

Main Methods:

  • A human MDR cancer cell line (NCI/ADR-RES) was subjected to various freezing and thawing (F/T) conditions.
  • Calcein, a fluorescent dye, was used as a model drug to quantify intracellular drug uptake.
  • Cellular drug uptake was measured using a fluorescent calcein assay.

Main Results:

  • Freezing and thawing to -20°C increased calcein uptake by 70.1% in MDR cancer cells (P=0.0004).
  • Further freezing and thawing to -40°C resulted in an 118% increase in intracellular calcein uptake (P=0.009).
  • These findings indicate a significant enhancement of drug delivery following F/T treatment.

Conclusions:

  • The study supports the hypothesis that F/T can enhance intracellular drug delivery to MDR cancer cells.
  • Potential mechanisms include F/T-induced denaturation of MDR-associated proteins and/or increased membrane permeability.
  • F/T presents a potential novel strategy to overcome MDR and improve chemotherapy effectiveness.

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