MP19:Instrument-free and High-throughput Screening of Mutagenic/Carcinogenic DNA Sensitizing Drugs using Gold Nanoparticles and Functional DNAs

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Joong Hyun Kim and Bong Hyun Chung

BioNanotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South Korea

Phototoxic responses after administration of photosensitive pharmaceutics have been recognized as undesirable side effects, and predicting potential hazardous side effects is gaining importance as new drugs are introduced to the market. One of the most harmful influences of the photosensitive drugs is pyrimidine dimer sensitizing effect, because the frequency of the formation is highest among other DNA photolesions and they are the main cause of skin cancer. However, conventional methods for the dimer analysis, such as immunological assay, gel electrophoresis and chromatic assays are not feasible for a high throughput screening of the dimer sensitizing drugs because they are time consuming and require additional manipulations such as purification, radio-labeling, enzymatic digestion, or chemical modification of DNA. In this presentation, we report a colorimetric method to detect DNA photodimer and screening of the dimer photosensitizing drugs by the naked eye using gold nanoparticles and functional DNAs. The stability of gold nanoparticles (AuNPs) in a high ionic strength solution is maintained by straight ssDNA adsorbed physically on the AuNPs. However, we found that UV-irradiated DNA was less adsorptive onto gold nanoparticles because of a conformational change of UV-irradiated DNA and thus triggered aggregation of the gold nanoparticles resulting in red to purple color changes of the mixtures and allowing colorimetric detection of the DNA photodimers by the naked eye. We successfully applied the colorimetric dimer detecting method to visually qualify the photosensitizing effect of non-steroidal anti-inflammatory drugs in parallel within only ten minutes. Since our method does not require any chemical or biochemical treatments or special instruments for purifying and qualifying the DNA photolesions, it should provide a feasible tool to accelerate screening of a large number of drug candidates

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