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A Microfluidic-based Electrochemical Biochip for Label-free DNA Hybridization Analysis
Published on: September 10, 2014
Electrochemical investigation of the interaction between topotecan and DNA at disposable graphite electrodes
Gulsah Congur1, Arzum Erdem1, Fehmi Mese1
1Ege University, Faculty of Pharmacy, Analytical Chemistry Department, 35100 Bornova, Izmir, Turkey.
Abstract:
Topotecan (TPT) is a semisynthetic, water soluble analog of the plant alkaloid camptothecin which has been widely used for the treatment of ovarian and cervical cancers. To obtain better understanding on how it can affect DNA structure, electrochemical biosensor platforms for the investigation of TPT-double stranded DNA (dsDNA) interaction were developed for the first time in this study. The electrochemical detection of TPT, and TPT-dsDNA interaction were investigated at the surface of pencil graphite electrodes (PGEs) and single-walled carbon nanotube (SWCNT) modified PGEs by using differential pulse voltammetry (DPV). The changes at the oxidation signals of TPT and guanine were evaluated before/after each modification/immobilization step. An enhanced sensor response was obtained by using SWCNT-PGEs compared to unmodified PGEs with resulting limits of detection (LODs) for TPT as 0.51 μg/mL, 0.45 μg/mL, 0.37 μg/mL (130 pmol, 117 pmol, 96.5 pmol in a 110 μL sample, respectively) by using electrochemically pretreated PGE, unmodified PGE and SWCNT modified PGE. In addition, electrochemical impedance spectroscopy (EIS) measurements were performed for the purpose of modification of PGEs by using SWCNTs and the interaction process at the surface of SWCNT-PGEs by evaluating the changes at the charge transfer resistance (Rct).
Insights
Researchers developed novel electrochemical biosensors to study Topotecan (TPT) interactions with double-stranded DNA (dsDNA). Modified electrodes enhanced TPT detection, offering new insights into its DNA binding mechanisms for cancer treatment.
Area of Science:
- Electrochemistry
- Biosensor Technology
- Medicinal Chemistry
Background:
- Topotecan (TPT), a camptothecin analog, is a vital chemotherapeutic agent for ovarian and cervical cancers.
- Understanding TPT's interaction with double-stranded DNA (dsDNA) is crucial for optimizing its therapeutic efficacy.
- Electrochemical methods offer sensitive platforms for studying drug-DNA interactions.
Purpose of the Study:
- To develop and characterize novel electrochemical biosensor platforms for investigating TPT-dsDNA interactions.
- To evaluate the performance of pencil graphite electrodes (PGEs) and single-walled carbon nanotube (SWCNT) modified PGEs for TPT detection.
- To elucidate the impact of TPT on DNA structure and electrochemical signals.
Main Methods:
- Differential pulse voltammetry (DPV) was employed to detect TPT and TPT-dsDNA interactions.
- Single-walled carbon nanotube (SWCNT) modified PGEs were utilized to enhance sensor sensitivity.
- Electrochemical impedance spectroscopy (EIS) was used to analyze electrode modification and interaction mechanisms.
Main Results:
- SWCNT-modified PGEs demonstrated significantly enhanced sensor responses compared to unmodified PGEs.
- Achieved limits of detection (LODs) for TPT were as low as 0.37 μg/mL (96.5 pmol) using SWCNT-PGEs.
- Electrochemical signals of TPT and guanine showed distinct changes upon TPT-dsDNA interaction.
Conclusions:
- Novel SWCNT-modified PGEs provide a sensitive and effective platform for detecting TPT and studying its interaction with dsDNA.
- The developed biosensor advances our understanding of TPT's mechanism of action at the molecular level.
- This research contributes to the development of improved diagnostic tools for cancer therapy monitoring.
