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Platinum anticancer drug binding to DNA detected by thickness-shear-mode acoustic wave sensor
1Department of Chemistry, University of Toronto, Ontario, Canada.
Abstract:
Nucleic acid has been attached to the electrodes of thickness-shear-mode acoustic wave devices to produce a biosensor for platinum-based drugs. The decreases in series resonant frequency for interactions of DNA with both cis- and transplatin are indicative of two distinct kinetic processes. The results of a kinetic analysis are interpreted in terms of nucleic acid binding of the hydrolysis products of the two drugs. Concentration-dependent decreases of series resonant frequency show that the limit of detection for the drugs is approximately 10(-7) M. Motional resistance changes for nucleic acid-drug interactions also convey information regarding the chemistry of the macromolecules at the interface.
Insights
This study developed a biosensor using nucleic acid on acoustic wave devices to detect platinum-based drugs like cisplatin. The biosensor accurately identifies drug interactions and achieves a detection limit of approximately 10(-7) M.
Area of Science:
- Biomedical Engineering
- Analytical Chemistry
- Molecular Biology
Background:
- Platinum-based drugs are crucial in cancer chemotherapy.
- Accurate detection and characterization of drug interactions with biological molecules are essential for understanding efficacy and toxicity.
- Acoustic wave devices offer sensitive platforms for label-free biosensing.
Purpose of the Study:
- To develop and validate a biosensor for detecting platinum-based drugs using nucleic acid-functionalized acoustic wave devices.
- To investigate the kinetic interactions between DNA and platinum-based drugs (cisplatin and transplatin).
- To determine the limit of detection and analyze the interfacial chemistry during drug binding.
Main Methods:
- Immobilization of nucleic acid onto thickness-shear-mode acoustic wave device electrodes.
- Monitoring changes in series resonant frequency and motional resistance upon drug interaction.
- Kinetic analysis of drug-nucleic acid binding processes.
- Varying drug concentrations to establish the limit of detection.
Main Results:
- Nucleic acid attachment to acoustic wave devices enabled biosensing of platinum-based drugs.
- Distinct kinetic processes were observed for DNA interactions with both cis- and transplatin.
- The limit of detection for the drugs was determined to be approximately 10(-7) M.
- Changes in motional resistance provided insights into the interfacial chemistry of drug-macromolecule interactions.
Conclusions:
- Thickness-shear-mode acoustic wave devices functionalized with nucleic acid serve as effective biosensors for platinum-based anticancer drugs.
- The biosensor can differentiate between stereoisomers of platinum drugs based on their binding kinetics with DNA.
- The developed method offers a sensitive approach for quantifying platinum-based drugs and studying their interaction mechanisms at the molecular level.