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 Scopus citations

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

Keywords

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

ASJC Scopus subject areas

  • Biophysics
  • Biomedical Engineering
  • Biotechnology
  • Electrochemistry

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  • Cite this

    Kahanda, D., Chakrabarti, G., Mcwilliams, M. A., Boothman, D. A., & Slinker, J. D. (2016). Using DNA devices to track anticancer drug activity. Biosensors and Bioelectronics, 80, 647-653. https://doi.org/10.1016/j.bios.2016.02.026