title: Toward therapeutic effects evaluation of chronic myeloid leukemia drug: electrochemical platform for caspase-3 activity sensing.
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.
authors: State Key Lab of Analytical Chemistry for Life Science (MOE), School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, PR China.
authors: Shiwei
authors: S
authors: Zhou
authors: State Key Lab of Analytical Chemistry for Life Science (MOE), School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, PR China.
authors: Tingting
authors: T
authors: Zheng
authors: State Key Lab of Analytical Chemistry for Life Science (MOE), School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, PR China.
authors: Yangfan
authors: Y
authors: Chen
authors: State Key Lab of Analytical Chemistry for Life Science (MOE), School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, PR China.
authors: Jingjing
authors: J
authors: Zhang
authors: State Key Lab of Analytical Chemistry for Life Science (MOE), School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, PR China.
authors: Linting
authors: L
authors: Li
authors: State Key Lab of Analytical Chemistry for Life Science (MOE), School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, PR China.
authors: Feng
authors: F
authors: Lu
authors: State Key Lab of Analytical Chemistry for Life Science (MOE), School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, PR China. Electronic address: jjzhu@nju.edu.cn.
authors: Jun-Jie
authors: JJ
authors: Zhu
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015374:Biosensing Techniques / Q000295:instrumentation; D053148:Caspase 3 / Q000378:metabolism*; D045744:Cell Line, Tumor; D000069439:Dasatinib; D004354:Drug Screening Assays, Antitumor / Q000295:instrumentation*; D055664:Electrochemical Techniques / Q000295:instrumentation*; D004867:Equipment Design; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*
chemical_list: D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D053221:TNF-Related Apoptosis-Inducing Ligand; D013844:Thiazoles; D053148:Caspase 3; D000069439:Dasatinib
keywords: Alkaline phosphatase; Caspase-3; Chronic myeloid leukemia; Dasatinib; Electrochemical biosensor; TRAIL