Enzyme-Based Electrochemical Biosensor for Therapeutic
Drug Monitoring of Anticancer Drug Irinotecan
Version 2 2018-04-23, 18:49
Version 1 2018-04-23, 18:48
Posted on 2018-04-23 - 18:49
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.
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Alvau, Maria
Domenica; Tartaggia, Stefano; Meneghello, Anna; Casetta, Bruno; Calia, Giammario; Serra, Pier Andrea; et al. (2018). Enzyme-Based Electrochemical Biosensor for Therapeutic
Drug Monitoring of Anticancer Drug Irinotecan. ACS Publications. Collection. https://doi.org/10.1021/acs.analchem.7b04357
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AUTHORS (8)
MA
Maria
Domenica Alvau
ST
Stefano Tartaggia
AM
Anna Meneghello
BC
Bruno Casetta
GC
Giammario Calia
PS
Pier Andrea Serra
FP
Federico Polo
GT
Giuseppe Toffoli