Electrochemical Detection of Anti-Breast-Cancer Agents in Human Serum by Cytochrome P450-Coated Carbon Nanotubes

Abstract

We report on the electrochemical detection of anti-cancer drugs in human serum with sensitivity values in the range of 8–925 nA/μM. Multi-walled carbon nanotubes were functionalized with three different cytochrome P450 isoforms (CYP1A2, CYP2B6, and CYP3A4). A model used to effectively describe the cytochrome P450 deposition onto carbon nanotubes was confirmed by Monte Carlo simulations. Voltammetric measurements were performed in phosphate buffer saline (PBS) as well as in human serum, giving well-defined current responses upon addition of increasing concentrations of anti-cancer drugs. The results assert the capability to measure concentration of drugs in the pharmacological ranges in human serum. Another important result is the possibility to detect pairs of drugs present in the same sample, which is highly required in case of therapies with high side-effects risk and in anti-cancer pharmacological treatments based on mixtures of different drugs. Our technology holds potentials for inexpensive multi-panel drug-monitoring in personalized therapy.

A Linear Approach to Multi-Panel Sensing in Personalized Therapy for Cancer Treatment

“…With some drug pairs, CYPs will produce multiple peaks in the single cyclic voltammogram [8]. But with other drugs, as reported in [9], we cannot distinguish the contributions of each single drug within a mixture by using only one CYP-sensor, because the current peaks are given at the same potential. The solution to this problem is given by using several CYPs in a sensor array, in the right combination.…”

“…Our previous work [9] shows some examples of detection of drug pairs. In particular we measured the concentration variations of three anti-cancer compounds (Cyclophosphamide, Ifosfamide and Ftorafur) in presence of another compound, Etoposide.…”

“…In order to demonstrate the feasibility of the approach presented in this paper, we evaluate the coefficient matrix S for seven different systems. These systems are thought as if the single sensors tested in [9] were disposed in seven different sensor arrays. Fig.…”

“…In our previous work [9], we measured four anti-cancer drugs with four independent sensors in a wet lab. For each sensor we evaluated the sensitivity and limit of detection, as defined in [17].…”

“…Nevertheless in previous works [8], [9], we have shown that by choosing the right combination of CYPs, the simultaneous measurement of two drugs in the same sample is possible, even if it requires complex data analysis. In the development of a cytochrome biosensor array for multiple drug monitoring, proper strategies to distinguish the different drug contributions are therefore necessary to minimize the errors coming from the measurements [10].…”