Using DNA devices to track anticancer drug activity

Dimithree Kahanda, Gaurab Chakrabarti, Marc A. Mcwilliams, David A. Boothman, Jason D. Slinker

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

It is beneficial to develop systems that reproduce complex reactions of biological systems while maintaining control over specific factors involved in such processes. We demonstrated a DNA device for following the repair of DNA damage produced by a redox-cycling anticancer drug, beta-lapachone (β-lap). These chips supported ß-lap-induced biological redox cycle and tracked subsequent DNA damage repair activity with redox-modified DNA monolayers on gold. We observed drug-specific changes in square wave voltammetry from these chips at therapeutic ß-lap concentrations of high statistical significance over drug-free control. We also demonstrated a high correlation of this change with the specific ß-lap-induced redox cycle using rational controls. The concentration dependence of ß-lap revealed significant signal changes at levels of high clinical significance as well as sensitivity to sub-lethal levels of ß-lap. Catalase, an enzyme decomposing peroxide, was found to suppress DNA damage at a NQO1/catalase ratio found in healthy cells, but was clearly overcome at a higher NQO1/catalase ratio consistent with cancer cells. We found that it was necessary to reproduce key features of the cellular environment to observe this activity. Thus, this chip-based platform enabled tracking of ß-lap-induced DNA damage repair when biological criteria were met, providing a unique synthetic platform for uncovering activity normally confined to inside cells.

Original languageEnglish (US)
Pages (from-to)647-653
Number of pages7
JournalBiosensors and Bioelectronics
Volume80
DOIs
StatePublished - Jun 15 2016

Fingerprint

DNA Damage
Oxidation-Reduction
DNA
Catalase
Equipment and Supplies
DNA Repair
Pharmaceutical Preparations
Repair
Drug and Narcotic Control
Peroxides
Cells
Gold
Biological systems
Voltammetry
Monolayers
Enzymes
Neoplasms
Therapeutics

Keywords

  • Base-excision repair
  • Biosensor
  • DNA repair
  • Electrochemical sensor
  • Oxidative damage

ASJC Scopus subject areas

  • Biophysics
  • Biomedical Engineering
  • Biotechnology
  • Electrochemistry

Cite this

Using DNA devices to track anticancer drug activity. / Kahanda, Dimithree; Chakrabarti, Gaurab; Mcwilliams, Marc A.; Boothman, David A.; Slinker, Jason D.

In: Biosensors and Bioelectronics, Vol. 80, 15.06.2016, p. 647-653.

Research output: Contribution to journalArticle

Kahanda, D, Chakrabarti, G, Mcwilliams, MA, Boothman, DA & Slinker, JD 2016, 'Using DNA devices to track anticancer drug activity', Biosensors and Bioelectronics, vol. 80, pp. 647-653. https://doi.org/10.1016/j.bios.2016.02.026
Kahanda, Dimithree ; Chakrabarti, Gaurab ; Mcwilliams, Marc A. ; Boothman, David A. ; Slinker, Jason D. / Using DNA devices to track anticancer drug activity. In: Biosensors and Bioelectronics. 2016 ; Vol. 80. pp. 647-653.
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