期刊
JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY
卷 19, 期 12, 页码 7974-7981出版社
AMER SCIENTIFIC PUBLISHERS
DOI: 10.1166/jnn.2019.16866
关键词
Anti-Retroviral Drug; Cytochrome P450-3A4 Enzyme; Drug Metabolism; Electrochemical Biosensors; Indinavir; Palladium Telluride Quantum Dot
类别
资金
- South African Department of Science and Technology's (DST's) National Nanoscience Postgraduate Teaching and Training Platform (NNPTTP)
Indinavir is a first-generation HIV protease inhibitor anti-retroviral (ARV) drug. Due to interindividual differences in the rate of indinavir metabolism, clinicians and pharmacologists have expressed urgent need for sensor devices that will enable real time determination of appropriate dosage. In this study, an indinavir biosensor was developed by the functionalization of a cysteamine-modified gold (CystlAu) electrode with biocompatible core shell 3-mercaptopropionic acid (3-MPA)-capped palladium telluride quantum dot (PdTeQD) and the heme-thiolate cytochrome P450-3A4 (CYP3A4) enzyme. The PdTeQD was capped with 3-mercaptopropionic acid (3-MPA) to improve its reactivity, biocompatibility and thermal stability. Small angle X-ray scattering (SAXS) studies revealed that the 3-MPA-PdTeQD particles formed core shells with diameters of 4.7 nm. Fourier transformed infrared spectroscopy (FTIR) experiments confirmed the formation of 3-MPA-PdTeQD by the presence of specific COOH and CH2 FTIR signature bands. Ultraviolet-visible (UV-Vis) spectrophotometric analysis of the quantum dot, exhibited a broad characteristic band at 320 nm, corresponding to a band gap energy (Ey) value of 3.87 eV, indicating that the QD is a semiconducting material. Cyclic voltammetry (CV) responses of the biosensor (i.e., CYP3A413-MPA-PdTeQDICystlAu) indicated that 0.26 V was the suitable potential for measuring indinavir metabolism. The biosensor has a sensitivity, dynamic linear range (DLR) and limit of detection (LOD) values of 0.0218 A/nM, 0.0004-0.01 nM (i.e., 3 x 10 7 7 x 1 0 6 mg L 1) and 0.023 x 10 7 mg L 1, respectively, for indinavir. The LOD value was lower than the maximum plasma concentration (Cmax) value (0.13-8.6 mg L 1) of indinavir which is normally measure 8 h after intake. The low DLR value makes the biosensor suitable for application at point-of-care, where indinavir concentration is expected to be in ng L-1 level in physiological samples within a few minutes of the drug administration.
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