Therapeutic drug monitoring (TDM) aimed at developing personalized medicines is one of the main targets in current clinical oncology. Keeping toxicity to a minimal level while maximising bioavailability of chemotherapeutics to an optimal activity is a key priority in cancer therapy, due to the high toxicity of most drugs and the high risk of relapses.
The development of ‘point of care devices’ to be used directly by patients at home, allowing a tailored therapy protocol based on individual responses, is the ultimate goal. This is a challenge from many points of view, and the availability of simple systems for sample preparation and target detection, with high sensitivity and selectivity, are the main milestones to be reached.
Collaboration This PhD proposal is developed in the context of a multi-team and multidisciplinary project funded by AIRC, the Italian Research Association for Cancer Research for a total of 2M euros and coordinated by Dr Toffoli from the CRO in Aviano. The central objective of the main project is to develop portable, inexpensive, sensitive, fast, multiplexed, analytical devices, to assay circulating biomarkers and to monitor therapeutic drugs in clinical samples of body fluids from patients with different types of cancer.
The aim of this project is to develop novel imprinted nanomaterials with fluorescence or colorimetric properties and high molecular recognition characteristics to be used as components in sensors for therapeutic drug monitoring. The three target molecules are: Sunitinib, a tyrosine kinase inhibitor that is used for the treatment of renal cell carcinoma; SN-38 that is the active metabolite of irinotecan, a semisynthetic analogue of camptothecin, an inhibitor of topoisomerase I and used in the treatment of colon cancer; taxol, a mitotic inhibitor used to treat lung, ovarian, breast, and head and neck cancers. The main methods currently available to quantify these drugs in biological samples are based on LC-ESI-MS or HPLC-MS/MS, and also spectroscopic techniques, in particular UV for sunitinib, taxol and SN38, and fluorescence for SN38 and its prodrug irinotecan. These techniques require expensive instrumentation and specialised operators and causes significant complication with patients compliance. A selective and specific sensor for the rapid quantification of these drugs in human plasma has not been developed yet and this is what this research proposal wishes to address. The project is organised in three main objectives:
Obj 1: design and synthesis of functional monomers containing fluorescent or colorimetric units that lead to quenching or colour change upon binding with the target drug. Obj 2: Synthesis and characterisation of the nanomaterials. Obj 3: Scaling up of nanomaterials synthesis and preparation of sensor interfaces for the development of the prototypes. This part of the project will be carried out partly via the close collaboration with Prof Berti at the University of Trieste and COBIK, a Centre of Excellence in Sensors based in Slovania.
Training program This project is multidisciplinary and will provide the student with training opportunities in different areas, ranging from organic chemistry and material chemistry to engineering, with the development of prototype devices. In particular the specific training will focus on: synthesis and characterisation of small molecules, which will include analytical techniques such as 1H and 13C-NMR, UV-Vis spectroscopy, IR, HPLC, LC-MS, fluorescence spectroscopy; synthesis and characterisation of nanogels and thin films, which will involve radical polymerisation, RAFT polymerisation and use and understanding of instrumentations for the characterisation of polymers such as dynamic light scattering, fluorescence microscopy, AFM, TEM and gel permeation chromatography; development of interfaces for sensors, which will cover electronics, interfaces as well as quality control. The ideal candidate should have a Honours Master level degree in Chemistry or Pharmaceutical Chemistry with strong background in organic chemistry and polymer chemistry. Excellent knowledge of NMR is a key requirement. Interested candidates should send a cover letter and CV to Professor M. Resmini at email@example.com. Please include full transcript of exams and marks obtained in the CV. This position is not suitable for students with degrees in Pharmacology, Engineering or nanotechnology. Shortlisted candidates will be notified via email. Interviews will take place in the last week of February.
The studentship will cover tuition fees and provide an annual tax-free maintenance allowance for 3 years at Research Councils UK rates (£16,054 in 2015/16).
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