Fluorescent lipid based sensor for the detection of thymidinephosphorylase as tumor biomarker

5-Fluorouracil (5-FU) is a chemotherapic drug widely employed to treat a wide range of solid tumors.Unfortunately, it has a narrow therapeutic window and the level of its target enzymes in biologicalfluids of patients can vary considerably. On these premises, a new fluorescent lipid based sensor for thedetection of thymidine phosphorylase, one of the target enzymes of 5-FU, was developed, to optimizepatient treatment. Both cationic and anionic fluorescent liposomes containing both an amphiphile tail-tagged with a pyrene residue and a 5-FU derivative were investigated. The effect of the presence of a bulkyquencher (the bromine atom) covalently linked to the end of the alkyl chain of the anionic component onthe emission signal was also evaluated. The interaction of liposomes with the target enzyme induces theoccurrence of a fluorescent signal, at an extent that depends on the formulation, due to the variation ofthe excimer/monomer ratio. In particular, a promising specific result was obtained upon the interactionof the target enzyme with liposomes formulated with DOPC, the cationic fluorescent surfactant, the 5-FU derivative and 11-bromoundecaonic acid at 5/1/1/3 molar ratio. Langmuir compression isothermsallowed clarifying the influence of lipid organization on the response of the sensor.