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Quantum dots having molecularly imprinted nanoshell for recognition of antibiotics

Final Report Summary - QUANTUMDOTIMPRINT (Quantum dots having molecularly imprinted nanoshell for recognition of antibiotics)

The aim of the QUANTUMDOTIMPRINT (QDI) project was the design and development of novel quantum dots (QDs) with a molecularly imprinted polymer (MIP) nanoshell to enable tracking of drugs or their metabolites in biological samples (in blood or in urine). Monitoring the changes in the drug/metabolite ratio (e.g. between enalapril and enalaprilat) is important for studying process pathways as well as for assessing the effectiveness of drug administration.

Allopurinol and its active metabolite oxypurinol have been chosen to be the target analytes in the project. Allopurinol is a structural isomer of hypoxanthine (naturally occurring purine in human body) and is an inhibitor of xanthine oxidase. Xanthine oxidase is an enzyme responsible for the successive oxidation of hypoxanthine and xanthine resulting in the production of uric acid, the product of human purine metabolism. The primary use of allopurinol is to treat hyperuricemia (an excess of uric acid in blood plasma). Importantly, within two hours after oral administration allopurinol is rapidly metabolised to its active metabolite oxypurinol. Afterwards oxypurinol is slowly excreted by the kidneys over 18 to 30 hours.

In the QDI project, a QD was envisaged to be either the main sensing element or a referencing element within a QD-dye conjugate. In the project novel fluorescent receptors have been designed and synthesised and their photophysical properties were characterised in dimethylsulfoxide (DMSO) and phosphate buffered saline (PBS) mixtures. Already in the aqueous phase, the fluorescence receptors responded to the presence of oxypurinol. Their response was much less pronounced in the presence of allopurinol. Additionally, MIP microparticles, containing newly developed fluorescent receptor, were prepared using conventional grinding method. The microparticles showed significant response to the presence of oxypurinol and moderate response to allopurinol demonstrating their use in possible analysis. The MIP also showed better response when compared to its non-imprinted counterpart (NIP). In another approach, the nanoconjugates comprising of CdTe650 QDs and fluorescent functional dyes (naphyridine or triamine-pattern based) have been developed and their effectiveness towards the presence of cyclic guanosine monophosphate (cGMP) or oxypurinol was demonstrated in aqueous solutions. Moreover, thin polymeric nanoshells were prepared on CdTe QD surface in combination with numerous imprinting attempts. Currently, the studies are ongoing to optimise nanosensor response to the presence of oxypurinol in aqueous solutions.