Development of Copper Selenide Quantum Dots-Based Therapeutic Drug Monitoring Biosensors for Toremifene - A Breast Cancer Drug

Abstract

With rising knowledge of the effects on plasma concentration caused by allelic variations in the cytochrome P450 genes and other metabolic factors such as drug-drug or drug-food interactions, more attention is paid to the possibility of therapeutic drug monitoring (TDM). Thus, there is a rising demand for quick, low-cost and efficient equipment for drug targeting. For such devices, electrochemical biosensing techniques serve as a promising alternative. Toremifene is the chlorinated analogue of tamoxifen and is used for adjuvant antiestrogenic treatment for breast cancer and could serve as a candidate for TDM treatments. In this work, a proof of concept enzymatic electrochemical biosensor is developed for the detection of toremifene in aqueous solution. The biosensor uses water-soluble 6-mercaptopropinoic acid capped copper selenide quantum dots (6MHACuSe QDs) conjugated to a cysteamine selfassembled monolayer on a gold electrode. The 6MHACuSe QDs where further conjugated with CYP2C9 enzyme, which has shown to have a major part in the hydroxylation of toremifene (TOR) to form 4-hydroxytoremifene (4OH-TOR). The 6MHACuSe QDs where synthesized using a facile and rapid aqueous route. Results from synthesis of 3-mercaptiorproionic acid (3MPA) and mercaptosuccinic acid (MSA) capped copper selenide QDs, are also presented in the study and compared to the results of the 6MHA capped copper selenide QDs. X-ray diffraction analysis (XRD) confirmed formation of copper selenide species of nonstoichiometric form Cu2-xSe (for the 6MHA and 3MPA capped CuSe QDs) and ?-CuSe stoichiometric form (for the MSA capped CuSe QDs).