Toward therapeutic effects evaluation of chronic myeloid leukemia drug: electrochemical platform for caspase-3
Shiwei Zhou1, Tingting Zheng1, Yangfan Chen1
1State Key Lab of Analytical Chemistry for Life Science (MOE), School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, PR China.
Abstract:
In recent decades, advanced therapies and novel scientific drug evaluation systems for chronic myeloid leukemia (CML) treatment are very urgent due to its increasing morbidity. The combination of dasatinib with tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) was supposed to be effective for leukemia therapy. Taking full advantage of novel nano-biotechnology, we have developed a robust electrochemical cytosensing approach to profile the therapeutic effects of dasatinib and TRAIL by probing the activity of caspase-3 from apoptotic CML cells. The sensor was on a base of a glassy carbon electrode (GCE) modified with nano-materials composed of Au nanoparticles (AuNPs), poly(dimethyl diallyl ammonium chloride) (PDDA), and carbon nanotubes (CNTs). Then the platform immobilized the biotinylated DEVD-peptide (biotin-Gly-Asp-Gly-Asp-Glu-Val-Asp-Gly-Cys) via the strong bonding between AuNPs and the thiol group (Au-S bond). In particular, the sensor was then constructed with the environmentally friendly alkaline phosphatase (ALP) via the specific interaction between the biotin and streptavidin, and could retest detection indirectly for caspase-3 sensing by detecting the differential pulse voltammetry (DPV) signal of enzymatic catalysis product, ascorbic acid (AA). The results indicated that either dasatinib or TRAIL could successfully induce the apoptosis of CML cells, while the combination of dasatinib and TRAIL resulted in an improved therapeutic effect, suggesting a novel optimized strategy for CML therapy. This novel electrochemical sensing strategy exhibits attractive advantages of environmental benignity, simple performance, high stability, and may be readily expanded to evaluate other cancer therapeutic effects.
Insights
A new electrochemical sensor effectively measures the therapeutic impact of dasatinib and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) on chronic myeloid leukemia (CML) cells. Combining these drugs shows enhanced CML treatment effects.
Area of Science:
- Biotechnology
- Nanotechnology
- Electrochemistry
- Oncology
Background:
- Chronic myeloid leukemia (CML) treatment requires novel therapeutic strategies and drug evaluation systems due to increasing morbidity.
- The combination of dasatinib and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a potential therapy for leukemia.
- Developing sensitive and efficient methods to assess treatment efficacy is crucial.
Purpose of the Study:
- To develop a robust electrochemical cytosensing approach to profile the therapeutic effects of dasatinib and TRAIL on CML cells.
- To utilize nano-biotechnology for creating a sensor that probes caspase-3 activity in apoptotic CML cells.
- To evaluate the combined therapeutic effect of dasatinib and TRAIL for CML treatment.
Main Methods:
- Fabrication of a glassy carbon electrode (GCE) modified with Au nanoparticles (AuNPs), poly(dimethyl diallyl ammonium chloride) (PDDA), and carbon nanotubes (CNTs).
- Immobilization of biotinylated DEVD-peptide onto the modified GCE via Au-S bonding.
- Construction of the sensor with alkaline phosphatase (ALP) and detection of caspase-3 activity indirectly by measuring the differential pulse voltammetry (DPV) signal of ascorbic acid (AA).
Main Results:
- Both dasatinib and TRAIL individually induced apoptosis in CML cells.
- The combination of dasatinib and TRAIL demonstrated a significantly improved therapeutic effect compared to individual treatments.
- The developed electrochemical sensor exhibited environmental benignity, simple performance, and high stability.
Conclusions:
- The combination of dasatinib and TRAIL presents a novel and optimized strategy for CML therapy.
- The novel electrochemical sensing strategy is effective for evaluating cancer therapeutic effects.
- This approach offers a promising tool for personalized medicine in oncology.
