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Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays
Published on: September 19, 2018
Supramolecular fluorescence sensor array used for the analysis of tyrosine kinase inhibitors in biological fluids and
Hong-Ling Yi1, Ru-Pei Yang2, Qing Tang3
1School of Pharmaceutical Sciences, Guizhou University, Guiyang, 550025, China.
Abstract:
Tyrosine kinase inhibitors (TKIs) are commonly used in tumor targeting therapy. However, the rapid analysis of TKIs remains a significant challenge, especially in complex biological fluid environments. In this work, we have constructed a supramolecular fluorescence sensor array based on a cucurbituril-dye host-guest complex. The binding affinity between the three complexes and each TKI is different, resulting in different cross-response signals of the complexes to the fluorescence of each TKI. Combined with linear discriminant analysis(LDA), five kinds of TKIs can be well identified. The supramolecular fluorescence sensor array could accurately identify and distinguish the five TKIs in water and could classify mixtures containing different concentrations of TKIs in serum. The concentration and Factor 1 exhibited a good linear relationship and the detection limit (LOD) was as low as 10-7 mol L-1. The method has good reproducibility and stability. In addition, the differentiation of four clinical concentrations of first-generation TKIs further validated the potential application of arrays in drug monitoring. Finally, our proposed array enabled drug imaging in living cells. Our array platform provided the foundation for the rapid and easy monitoring of 4-anilinoquinazoline TKIs.
Insights
A new supramolecular fluorescence sensor array can rapidly identify and monitor tyrosine kinase inhibitors (TKIs) in biological fluids. This sensor array shows potential for drug monitoring and imaging in living cells.
Area of Science:
- Analytical Chemistry
- Supramolecular Chemistry
- Biomedical Engineering
Background:
- Tyrosine kinase inhibitors (TKIs) are crucial in cancer therapy.
- Rapid and accurate analysis of TKIs in biological fluids is challenging.
Purpose of the Study:
- To develop a supramolecular fluorescence sensor array for TKI detection.
- To enable rapid identification and quantification of TKIs in complex matrices.
Main Methods:
- Construction of a supramolecular fluorescence sensor array using cucurbituril-dye host-guest complexes.
- Utilizing differential binding affinities and cross-response signals.
- Applying linear discriminant analysis (LDA) for data interpretation.
Main Results:
- Accurate identification and differentiation of five TKIs in water and serum mixtures.
- Achieved a low detection limit (LOD) of 10-7 mol L-1.
- Demonstrated potential for drug imaging in living cells and monitoring clinical TKI concentrations.
Conclusions:
- The developed sensor array offers a robust platform for rapid and sensitive TKI analysis.
- This technology has significant implications for therapeutic drug monitoring and personalized medicine.
- The array provides a foundation for the easy monitoring of 4-anilinoquinazoline TKIs.
