Enzymatic and Nonenzymatic Electrochemical Interaction of Abiraterone (Antiprostate Cancer Drug) with Multiwalled Carbon Nanotube Bioelectrodes

Abstract

Unexplored electrochemical behavior of abiraterone, a recent and widely used prostate cancer drug, in interaction with cytochrome P450 3A4 (CYP3A4) enzyme and multiwalled carbon nanotubes (MWCNTs) is investigated in this work. The results reported in this work are significant for personalized medicine and point-of-care chemical treatment, especially to improve the life expectancy and quality of life of patients with prostate-cancer. To this purpose, enzymatic and nonenzymatic electrochemical biosensors were developed and characterized with different concentrations of abiraterone. Nonenzymatic biosensors were functionalized with MWCNTs as a catalyst for signal enhancement, while enzymatic biosensors have been obtained with CYP3A4 protein immobilized on MWCNTs as recognition biomolecule. Enzymatic electrochemical experiments demonstrated an inhibition effect on the CYP3A4, clearly observed as a diminished electrocatalytic activity of the enzyme. Electrochemical responses of nonenzymatic biosensors clearly demonstrated the direct electroactivity of abiraterone when reacting with MWCNT as well as an electrode-fouling effect.

Recent Advances in Electrochemical Biosensors Based on Enzyme Inhibition for Clinical and Pharmaceutical Applications

“…Later, MCNWTs were used for CYP3A4 sensor design. The enzymatic biosensor was employed for the study of abiraterone, a drug used in prostate cancer therapy [ 20 ]. The sensing system has been optimized and the investigations showed that the inhibition was irreversible when the concentration of abiraterone exceeded 1 µM.…”

“…These drug targets act as enzyme inhibitors; consequently, the inhibitor concentration affecting the rate of this enzymatic transformation can be measured. Electrochemical biosensors perform measurements using small sample volumes, low concentrations of biological components and sometimes miniaturized analytical devices [ 20 , 21 , 22 , 23 , 24 ].…”

Metallodendrimer‐sensitised Cytochrome P450 3A4 Electrochemical Biosensor for TB Drugs

“…An enzymatic biosensor will be able to mimic the body's natural metabolism of these drugs or substrates, however, not much literature is available for CYP biosensors for TB drug detection. CYP3A4 has been combined with multi-walled carbon nanotubes to form a biosensor for detection of an inhibitor such as abiraterone [9]. Another inhibitor indinavir was also detected with the aid of didodecyldimethylammonium bromide (DDAB) vesicular system [10].…”

Interaction of the Anticancer Drug Abiraterone with dsDNA

“…Рак предстательной железы является одним из наиболее распространённых онкологических заболеваний. Фармакотерапия этого заболевания направлена на снижение уровня андрогенов за счёт использования ингибиторов цитохрома P450 17А1 (17α-гидроксилазы, 17,20-лиазы) как ключевого фермента биосинтеза андрогенов, а также на блокирование взаимодействия андрогенов с рецепторами андрогенов опухолевых клеток [18][19][20][21][22][23][24][25][26][27].…”

“…Абиратерон (рис. 1) широко используют для лечения пациентов, страдающих метастазирующим кастрационнорезистентным раком предстательной железы; при его приёме в форме ацетата абиратерона (АА) в дозе 1000 мг/ день наблюдается снижение уровня тестостерона до <50 нг/ мл, что приводит к сокращению пролиферации опухолевых клеток, чувствительных к тестостерону [24][25][26]. Несмотря на активное использование абиратерона в медицинской практике, фармакологические мишени этого препарата недостаточно исследованы, за исключением ряда изоформ цитохрома P450 (21A2, 51A1, 11A1, 11B2, 19A1, 3A4, 2D6, 2C8), а также 3β-гидроксистероиддегидрогеназы [19][20][21].…”