Nanostructured SERS-electrochemical biosensors for testing of anticancer drug interactions with DNA Hoda Ilkhani a , Taylor Hughes a , Jing Li b , Chuan Jian Zhong b , Maria Hepel a,n a Department of Chemistry, State University of New York at Potsdam, Potsdam, NY 13676, USA b Department of Chemistry, State University of New York at Binghamton, Binghamton, NY 13902, USA article info Article history: Received 13 December 2015 Received in revised form 26 January 2016 Accepted 28 January 2016 Available online 29 January 2016 Keywords: SERS/electrochemical biosensor Breast cancer Doxorubicin Chemotherapeutic drug screening DNA biosensor Genosensor abstract Widely used anti-cancer treatments involving chemotherapeutic drugs result in cancer cell damage due to their strong interaction with DNA. In this work, we have developed laboratory biosensors for screening chemotherapeutic drugs and to aid in the assessment of DNA modification/damage caused by these drugs. The sensors utilize surface-enhanced Raman scattering (SERS) spectroscopy and electrochemical methods to monitor sensory film modification and observe the drug-DNA reactivity. The self-assembled monolayer protected gold-disk electrode (AuDE) was coated with a reduced graphene oxide (rGO), de- corated with plasmonic gold-coated Fe 2 Ni@Au magnetic nanoparticles functionalized with double- stranded DNA (dsDNA), a sequence of the breast cancer gene BRCA1. The nanobiosensors AuDE/SAM/ rGO/Fe 2 Ni@Au/dsDNA were then subjected to the action of a model chemotherapeutic drug, doxorubicin (DOX), to assess the DNA modification and its dose dependence. The designed novel nanobiosensors offer SERS/electrochemical transduction, enabling chemically specific and highly sensitive analytical signals generation. The SERS measurements have corroborated the DOX intercalation into the DNA duplex whereas the electrochemical scans have indicated that the DNA modification by DOX proceeds in a concentration dependent manner, with limit of detection LOD ¼8 mg/mL (S/N ¼3), with semilog linearity over 3 orders of magnitude. These new biosensors are sensitive to agents that interact with DNA and facilitate the analysis of functional groups for determination of the binding mode. The proposed nano- biosensors can be applied in the first stage of the drug development for testing the interactions of new drugs with DNA before the drug efficacy can be assessed in more expensive testing in vitro and in vivo. & 2016 Elsevier B.V. All rights reserved. 1. Introduction Extensive investigations have recently been carried out to de- velop new anti-cancer drugs for treatment of this widespread disease killing millions of people annually. Chemotherapy, photo- dynamic therapy, and hyperthermic therapy remain some of the most widely applied treatments (Burgess, 2012; Du et al., 2015; Yang et al., 2015). Particular attention in studies of new anticancer drugs has been paid to increase the drug efficacy toward killing cancer cells while limiting their devastating effects on healthy cells through the targeted approach based on cancer cell biorecognition strategy (Holohan et al., 2013; Tacar et al., 2013). In this work, we have focused on the development of a laboratory nanobiosensor for screening of anticancer drugs. The sensor utilizes surface-en- hanced Raman scattering (SERS) spectroscopy and electrochemical relaxation techniques, enabling the assessment of anticancer drug interactions with DNA bound to the nanostructured SERS/elec- trochemical biosensor surface. While SERS biosensors have been extensively investigated owing to their high sensitivity and che- mical identification capabilities (see excellent reviews: (Baia 2012; Bantz et al., 2011; Huh et al., 2009)), the SERS studies of drug in- teractions with DNA have been scarce (Beljebbar et al., 1995; Lee et al., 2004; Li et al., 2015; Stanicová et al., 1999) and we have not found any reports on nanostructured SERS/electrochemical bio- sensors designed specifically for that purpose. Perspective analy- tical applications of novel SERS nanostructures have recently been reviewed (Li et al., 2015; Tokonami et al., 2012; Tripp et al., 2008). The detection of DNA damage is the key challenge in studies of mutations, carcinogenesis, and aging (Hepel et al., 2012b). The use of the sophisticated instrumentation necessary for DNA analysis, such as the mass spectrometry, poses a problem in small labs around the world due to the high cost and the requirement of highly qualified personnel. This problem is effectively addressed by the new wave of nanobiosensors which can provide high sen- sitivity, low detection limit, and ease of use to these measure- ments. Thus, the DNA biosensors became an important tool in Contents lists available at ScienceDirect journal homepage: www.elsevier.com/locate/bios Biosensors and Bioelectronics http://dx.doi.org/10.1016/j.bios.2016.01.068 0956-5663/& 2016 Elsevier B.V. All rights reserved. n Corresponding author. E-mail address: hepelmr@potsdam.edu (M. Hepel). URL: http://www2.potsdam.edu/hepelm (M. Hepel). Biosensors and Bioelectronics 80 (2016) 257–264