Designing a multi-panel biochip based on P450 and CNT for drugs monitoring in personalized therapy

***Archived: This is a past project,  it is not on offer at the moment!***

Introduction


In these last years it has been recognized that any drug therapy needs to be modified according to the individual patient, leading to the personalization of the pharmacological treatment. It has been reported that the response rate of patients to drugs used in major diseases, is typically in the 20% to 50% range. This is because of the protein’s polymorphism in metabolism that can cause over-dosing or under-dosing in hospitalized patients and in some cases can lead to adverse drug reactions. This is especially true for main common diseases, i.e. heart diseases, diabetes and cancer. Currently it is being increasingly recognized  that drug therapy needs to be selected and modified according to the individual patient leading to the “individualization” or “personalization” of the therapy. There are many reasons why a patient might or might not respond to a drug or be affected by an adverse event. Among these are missed doses, drug-to–drug interactions, drug allergies and medication errors. But the major reason for inappropriate drug response has to be found in the genetic polymorphism of the proteins involved in drug metabolism. The best solution should be to measure drugs metabolism directly in the patient blood.

 

The Master Project
Aim of this master project is to investigate a new technology to measure drugs metabolism directly in the patient blood. Towards this aim, the project was focused on the design of a biochip based on cytochrome P450 and carbon nanotubes for the detection of drugs used for breast-cancer therapy. Four drugs used in chemotherapy treatments of this kind of tumour were selected: Cyclophosphamide, Etoposide, Ftorafur and Ifosfamide. The cytochromes P450 involved in the metabolism of these drugs were analyzed and it was thought to use them as the biological-recognition elements of an amperometric biosensor for drug detection. Three isoforms of cytochrome P450, CYP1A2, CYP2B6 and CYP3A4 were deposited for drop-casting onto graphite electrodes functionalized with multi-walled carbon-nanotubes. Carbon-nanotubes were used to improve the electron transfer between the electrode and the protein. These nano-structured electrodes were used for the electrochemical detection of the selected drugs through cyclic voltammetry measurements. In cyclic voltammetry analysis, the drug concentration is detected and quantified by the measurement of current peaks obtained by applying a potential variable in time.

Tasks:


  • Nano-structuring electrochemical electrodes with carbon nanotubes
  • Bio-functionalize the nano-structured electrodes with the proteins P450

  • Acquiring electrochemical signals from the nano-structures

  • Computing the sensing performances obtained by nano-structuring

Requirements:


  • Basic knowledge on sensors
  • 
Basic Knowledge on nanotechnology
  • Experience with electrical measurements with lab equipments

  • Interest in diagnostics for personalized therapy
     

This project was supervised by Dr. Sandro Carrara.

 

***Archived: This is a past project,  it is not on offer at the moment!***