Development of Metal Oxide Based New Nanobiosensors for Determination of DNA Interaction with Anticancer Drugs
Project no. 26309 · Status: Kapanmış (Yayın bekleniyor) · 2022
Summary
<p>Nanometer-sized metal oxide nanoparticles (MONPs) have become increasingly significant in recent years as materials that provide effective surfaces for biomolecular sensing. Due to their superior optical, electrical, and molecular properties, MONPs contribute to the development of novel sensor systems by ensuring the expected functionality on the biosensor surface and enhancing signal amplification.</p><p>In this thesis, sensitive bioanalytical applications were conducted using electrochemical biosensors designed for the determination of interactions between DNA and cancer cells (MCF-7) with the anticancer drugs Mitomycin C (MC) and Daunorubicin (DNR). These biosensors were developed using disposable pencil graphite electrodes (PGE) modified with ZnO or Al-doped ZnO (Al-ZnO) MONPs.</p><p>In the first section, ZnO and Al-ZnO metal oxide nanomaterials were modified onto electrode surfaces, and the optimal conditions for each nanomaterial that provided the highest signal amplification were determined. This process laid the groundwork for the development of disposable DNA biosensor platforms by measuring the guanine response in DNA using differential pulse voltammetry (DPV).</p><p>In the second section of the study, disposable biosensors modified with ZnO or Al-ZnO were designed for the voltammetric determination of the interaction between DNA and the anticancer drug Mitomycin C. Additionally, two disposable nanobiosensor systems modified with ZnO and Al-ZnO were developed to analyze the interaction of this drug with cancer cells (MCF-7). These interactions were investigated using cyclic voltammetry (CV) and DPV methods.</p><p>In the third section, ZnO- or Al-ZnO-modified PGE-based nanobiosensors were developed for the electrochemical analysis of the interaction between DNA and the anticancer drug Daunorubicin (DNR). Subsequently, two additional nanobiosensor systems modified with ZnO and Al-ZnO MONPs were designed to determine the interaction of DNR with MCF-7 cancer cells.</p><p>In the final section of the thesis, interaction analyses of DNA-drug and cell-drug systems in solution were performed using the developed nanobiosensors. The interactions of single-stranded probe DNA and double-stranded hybrid DNA with anticancer drugs were investigated, and efforts were made to translate the nanobiosensor system into a diagnostic kit. Furthermore, the developed systems were tested in real sample applications using commercial MC and DNR drug samples, and analyses were carried out using electrochemical techniques.</p><p>Consequently, MONP-based sensitive nanobiosensor platforms were developed in this thesis. DNA-drug and cancer cell-drug interactions were analyzed using these disposable systems, which are rapid, easy to prepare and use, and miniaturizable. This study enabled label-free, direct analysis of DNA-drug and cell-drug interactions using DNA/cancer cells immobilized onto the electrode surface without the need for labeling agents, indicators, or biomarkers. In addition, if the nanobiosensor is converted into a diagnostic kit, disposable, portable and rapid analysis platforms can be provided for clinical applications by healthcare personnel as an alternative to the traditional methods used today.</p>