Detection of the level of DNA cross-linking with cisplatin by electrochemical quartz crystal microbalance

Abstract

Biosensors based on DNA self-assembled monolayers (DNA-SAMs) combined with electrochemical transducers have shown great potential to serve an important role in simple, accurate and inexpensive genetic analysis relevant to many fields. Recently we have reported on observing a significant change in the viscoelasticity of such DNA layers immobilized on gold electrodes, upon redox switching of certain metal complexes at a millisecond time scale using an electrochemical quartz crystal microbalance (EQCM). In this study we have performed chronoamperometry on single stranded and double stranded DNA/6-mercapto-1-hexanol (MCH) mixed SAMs on gold electrodes in the presence of hexaammineruthenium(III) (RuHex) to monitor the DNA modification with cis-diamminedichloroplatinum(II) (cisplatin). Our EQCM studies confirmed that the redox response of electrostatically bound RuHex is capable of providing quantitative information regarding the extent of DNA cross-linking with cisplatin. We believe that this method can be used in studies to test the interactions of cancer chemotherapeutic medications like cisplatin with ss & dsDNA and ultimately be a new technology for rapid screening of such potential drug candidates that are able to penetrate the blood-brain barrier and interact with DNA in order to inhibit cancer cell growth of brain tumor tissue by forming DNA adducts.