Publication
Reliable, low cost, and accessible drug monitoring systems for individualized healthcare, especially chemotherapy for malignant diseases like prostate cancer and AIDS, are highly desira-ble. This is even more critical for drugs like abiraterone and TFV, with very narrow and low (submi-cro-molar) therapeutic windows. Point-of-care biosensors for drug monitoring offer a solution for this kind of therapy: bringing treatments to the patientâs bedside and eliminating interfering factors in medical treatments like interindividual differences (genetic profile, age, race, gender, etc.), environmental agents and the influences of other drugs (drug-drug interactions, adverse effects, etc.). Moreover, point-of-care biosensors provide access to reliable, fast and cheap cutting-edge technology for a large popula-tion. In particular, such a novel chemical therapy will suppress the morbidity rate and treatment time, as well as providing better screening of patients, and tighter monitoring of treatment. Con-sequently, this would lead to an improvement in patientsâ medical treatments and overall quality of life. In other words, improved treatment efficacy and less side effects for patients. The objective of this thesis is to investigate biosensors for the monitoring of drugs for chemother-apeutic treatment for prostate cancer and AIDS. The first part of this work is devoted to the devel-opment of biosensors to target three main groups of drugs : electroactive drugs, drugs that involve an enzyme in their metabolic pathway and drugs that are neither electroactive nor interact with enzymes in the body. The second part is devoted to offering a reliable solution for selective and sensitive point-of-care biosensing for anti-prostate cancer drugs and anti-AIDS drugs. Screen-printed based biosensors with nanofunctionalization are offered for electroactive drug detection as a solution for prostate-cancer personalized medicine. Several steps of optimization have been performed to boost their electrochemical performance towards detection of Etoposide (a prostate cancer drug) in its therapeutic range, and also preparing the biosensor for the devel-opment of an enzymatic biosensor. Furthermore, they have been used to observe the quantum blockage in gold nanoparticles, and to investigate its impact on the biosensing performance. Secondly, an enzymatic biosensor for monitoring drugs, which involve cytochrome P450 enzymes in their metabolic pathway in the body, is presented as a second solution for prostate-cancer per-sonalized medicine. This kind of sensor is produced by immobilizing the cytochrome P450 enzyme over the already-mentioned optimized biosensor. The biosensor is utilized for investigating abi-raterone electrochemistry, and subsequently the detection of abiraterone in buffer and human serum are reported for the first time. Finally, affinity-based biosensors are proposed to address the detection of drugs that are neither electroactive nor interact with enzymes in body. Tenofovir, an anti-HIV drug, is targeted in this case to help find also a solution for HIV personalized medicine. To this aim, an aptamer-based sensing surface is obtained and optimized after intensive optimiza-tion, and the experimental testing of different possible surfaces. This surface is formed on the ac-tive part of a field-effect transistor transducer, and also a memristive nanowire transducer as a recognition element to develop the affinity based biosensors.
Christoph Merten, Ngoc Hien Du
Li Tang, Yugang Guo, Yang Zhao