Enzyme-Based Electrochemical Biosensor for Therapeutic Drug Monitoring of Anticancer Drug Irinotecan.
Maria Domenica AlvauStefano TartaggiaAnna MeneghelloBruno CasettaGiammario CaliaPier Andrea SerraFederico PoloGiuseppe ToffoliPublished in: Analytical chemistry (2018)
Therapeutic drug monitoring (TDM) is the clinical practice of measuring pharmaceutical drug concentrations in patients' biofluids at designated intervals, thus allowing a close and timely control of their dosage. To date, TDM in oncology can only be performed by trained personnel in centralized laboratories and core facilities employing conventional analytical techniques (e.g., MS). CPT-11 is an antineoplastic drug that inhibits topoisomerase type I, causing cell death, and is widely used in the treatment of colorectal cancer. CPT-11 was also found to directly inhibit acetylcholine esterase (AChE), an enzyme involved in neuromuscular junction. In this work, we describe an enzymatic biosensor, based on AChE and choline oxidase (ChOx), which can quantify CPT-11. ACh (acetylcholine) substrate is converted to choline, which is subsequently metabolized by ChOx to give betaine aldehyde and hydrogen peroxide. The latter one is then oxidized at a suitably polarized platinum electrode, providing a current transient proportional to the amount of ACh. Such an enzymatic process is hampered by CPT-11. The biosensor showed a ∼60% maximal inhibition toward AChE activity in the clinically relevant concentration range 10-10 000 ng/mL of CPT-11 in both simple (phosphate buffer) and complex (fetal bovine serum) matrixes, while its metabolites showed negligible effects. These findings could open new routes toward a real-time TDM in oncology, thus improving the therapeutic treatments and lowering the related costs.
Keyphrases
- hydrogen peroxide
- gold nanoparticles
- label free
- cell death
- sensitive detection
- end stage renal disease
- nitric oxide
- clinical practice
- quantum dots
- palliative care
- ms ms
- chronic kidney disease
- ejection fraction
- drug induced
- newly diagnosed
- peritoneal dialysis
- resistance training
- prognostic factors
- multiple sclerosis
- minimally invasive
- patient reported outcomes
- emergency department
- blood pressure
- high resolution
- combination therapy
- carbon nanotubes
- ionic liquid
- patient reported