Core-Shell Palladium Telluride Quantum Dot-Hemethiolate Cytochrome Based Biosensor for Detecting Indinavir Drug.

Abstract

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 (Cyst|Au) 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 (Eg) value of 3.87 eV, indicating that the QD is a semiconducting material. Cyclic voltammetry (CV) responses of the biosensor (i.e., CYP3A4|3-MPA-PdTeQD|Cyst|Au) 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 μA/nM, 0.0004-0.01 nM (i.e., 3×10-7 -7×10-6 mg L-1) and 0.023×10-7 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.