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Nanostructured SERS-electrochemical biosensors for testing of anticancer drug interactions with DNA
Hoda Ilkhani1, Taylor Hughes1, Jing Li2
1Department of Chemistry, State University of New York at Potsdam, Potsdam, NY 13676, USA.
Abstract:
Widely used anti-cancer treatments involving chemotherapeutic drugs result in cancer cell damage due to their strong interaction with DNA. In this work, we have developed laboratory biosensors for screening chemotherapeutic drugs and to aid in the assessment of DNA modification/damage caused by these drugs. The sensors utilize surface-enhanced Raman scattering (SERS) spectroscopy and electrochemical methods to monitor sensory film modification and observe the drug-DNA reactivity. The self-assembled monolayer protected gold-disk electrode (AuDE) was coated with a reduced graphene oxide (rGO), decorated with plasmonic gold-coated Fe2Ni@Au magnetic nanoparticles functionalized with double-stranded DNA (dsDNA), a sequence of the breast cancer gene BRCA1. The nanobiosensors AuDE/SAM/rGO/Fe2Ni@Au/dsDNA were then subjected to the action of a model chemotherapeutic drug, doxorubicin (DOX), to assess the DNA modification and its dose dependence. The designed novel nanobiosensors offer SERS/electrochemical transduction, enabling chemically specific and highly sensitive analytical signals generation. The SERS measurements have corroborated the DOX intercalation into the DNA duplex whereas the electrochemical scans have indicated that the DNA modification by DOX proceeds in a concentration dependent manner, with limit of detection LOD=8 µg/mL (S/N=3), with semilog linearity over 3 orders of magnitude. These new biosensors are sensitive to agents that interact with DNA and facilitate the analysis of functional groups for determination of the binding mode. The proposed nanobiosensors can be applied in the first stage of the drug development for testing the interactions of new drugs with DNA before the drug efficacy can be assessed in more expensive testing in vitro and in vivo.
Insights
Researchers developed novel nanobiosensors using SERS and electrochemistry to screen chemotherapy drugs and assess their DNA interactions. These sensors detect drug-induced DNA damage, aiding early-stage drug development.
Area of Science:
- Nanotechnology
- Biosensing
- Analytical Chemistry
Background:
- Chemotherapeutic drugs damage cancer cells via DNA interaction.
- Assessing drug-DNA interactions is crucial for drug development.
- Existing methods for assessing DNA damage can be costly and time-consuming.
Purpose of the Study:
- To develop novel nanobiosensors for screening chemotherapeutic drugs.
- To assess DNA modification and damage caused by drugs.
- To enable sensitive and specific detection of drug-DNA interactions.
Main Methods:
- Utilized surface-enhanced Raman scattering (SERS) spectroscopy and electrochemical methods.
- Developed a nanobiosensor comprising a gold-disk electrode (AuDE), reduced graphene oxide (rGO), and DNA-functionalized magnetic nanoparticles.
- Tested the nanobiosensor with doxorubicin (DOX) to assess DNA modification.
Main Results:
- Demonstrated SERS/electrochemical transduction for chemically specific signals.
- Corroborated doxorubicin intercalation into DNA using SERS.
- Indicated concentration-dependent DNA modification by doxorubicin with a limit of detection (LOD) of 8 µg/mL.
Conclusions:
- The developed nanobiosensors are sensitive to DNA-interacting agents.
- The sensors facilitate analysis of functional groups and binding modes.
- These biosensors can be applied in early-stage drug development for DNA interaction testing.
