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    Fluorescent lipid based sensor for the detection of thymidine phosphorylase as tumor biomarker

    Year: 2017

    Journal: Sens. Actuator B-Chem., Volume 245, JUN, page 213–220

    Authors: Petaccia, Manuela; Giansanti, Luisa; Leonelli, Francesca; La Bella, Angela; Villalva, Denise Gradella; Mancini, Giovanna

    Organizations: PRIN project Multinanoita [2010JMAZML]; FIRB [2012RBFR12BGHO]; Ciencia sem Fronteiras; CAPES Foundation

    Keywords: Liposomes; Excimer; Thymidine phosphorylase; Surface charge; Quenching; Langmuir isotherms

    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 biological fluids of patients can vary considerably. On these premises, a new fluorescent lipid based sensor for the detection of thymidine phosphorylase, one of the target enzymes of 5-FU, was developed, to optimize patient 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 bulky quencher (the bromine atom) covalently linked to the end of the alkyl chain of the anionic component on the emission signal was also evaluated. The interaction of liposomes with the target enzyme induces the occurrence of a fluorescent signal, at an extent that depends on the formulation, due to the variation of the excimer/monomer ratio. In particular, a promising specific result was obtained upon the interaction of 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 isotherms allowed clarifying the influence of lipid organization on the response of the sensor. (C) 2017 Elsevier B.V. All rights reserved.
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