Development of Label-Free Impedimetric Immunosensors for IKZF1 and IKZF3 Femtomolar Detection for Monitoring Multiple Myeloma Patients Treated with Lenalidomide

Abstract

AbstractLenalidomide is an immunomodulatory drug (IMiD) used to treat multiple myeloma (MM) patients. Lenalidomide destroys MM cells by inducing ubiquitination and the consequent degradation of Ikaros family zinc finger proteins 1 and 3 (IKZF1 and IKZF3). High expression of IKZF1 and IKZF3 in MM results in less sensitivity to lenalidomide treatment and possible cytotoxic effect. Therefore, detecting the expression of IKZF1 and IKZF3 proteins is of utmost importance in the treatment of MM. Here, we report the fabrication of a novel label-free electrochemical immunosensor for the rapid detection and quantification of IKZF1 and IKZF3 using electrochemical impedance spectroscopy (EIS). Gold electrodes were used to fabricate the immunosensors by immobilizing IKZF1 and IKZF3 specific antibodies using cysteamine and PDITC crosslinkers. The immunosensors were able to detect IKZF1 and IKZF3 protein levels with respective low detection limits of 0.68 and 0.97 pg/ml (11.8 and 16.7 fM). Furthermore, the immunosensors’ successful application in human serum and their high selectivity and sensitivity enables their possible application in other biofluids as simple point-of-care devices for monitoring multiple myeloma patients treated with lenalidomide, to prevent the drug’s cytotoxicity and minimize its side effects.