Using DNA devices to track anticancer drug activity

Biosensors & Bioelectronics
Dimithree KahandaJason D Slinker

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,...Continue Reading

Citations

Jan 25, 2017·International Journal of Radiation Biology·Muhammad Torequl Islam
Aug 12, 2018·Biosensors & Bioelectronics·Dimithree KahandaJason D Slinker
May 2, 2018·Journal of Medicinal Chemistry·Kuojun ZhangSheng Jiang
Dec 30, 2017·Analytical Chemistry·Dimithree KahandaJason D Slinker

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Biosensors are devices that are designed to detect a specific biological analyte by essentially converting a biological entity (ie, protein, DNA, RNA) into an electrical signal that can be detected and analyzed. The use of biosensors in cancer detection and monitoring holds vast potential. Biosensors can be designed to detect emerging cancer biomarkers and to determine drug effectiveness at various target sites. Biosensor technology has the potential to provide fast and accurate detection, reliable imaging of cancer cells, and monitoring of angiogenesis and cancer metastasis, and the ability to determine the effectiveness of anticancer chemotherapy agents.

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