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dc.contributor.authorBoltersdorf, T-
dc.contributor.authorAnsari, J-
dc.contributor.authorSenchenkova, E-
dc.contributor.authorGroeper, J-
dc.contributor.authorPajonczyk, D-
dc.contributor.authorVital, S-
dc.contributor.authorKaur, G-
dc.contributor.authorAlexander, J-
dc.contributor.authorVogl, T-
dc.contributor.authorRescher, U-
dc.contributor.authorLong, N-
dc.contributor.authorGavins, F-
dc.identifier.citationTheranostics, 2020, 10(15): 6599 - 6614en_US
dc.description.abstract© The author(s). Inflammatory conditions are associated with a variety of diseases and can significantly contribute to their pathophysiology. Neutrophils are recognised as key players in driving vascular inflammation and promoting inflammation resolution. As a result, neutrophils, and specifically their surface formyl peptide receptors (FPRs), are attractive targets for non-invasive visualization of inflammatory disease states and studying mechanistic details of the process. Methods: A small-molecule Formyl Peptide Receptor 2 (FPR2/ALX)-targeted compound was combined with two rhodamine-derived fluorescent tags to form firstly, a targeted probe (Rho-pip-C1) and secondly a targeted, pH-responsive probe (Rho-NH-C1) for in vivo applications. We tested internalization, toxicity and functional interactions with neutrophils in vitro for both compounds, as well as the fluorescence switching response of Rho-NH-C1 to neutrophil activation. Finally, in vivo imaging (fluorescent intravital microscopy [IVM]) and therapeutic efficacy studies were performed in an inflammatory mouse model. Results: In vitro studies showed that the compounds bound to human neutrophils via FPR2/ALX without causing internalisation at relevant concentrations. Additionally, the compounds did not cause toxicity or affect neutrophil functional responses (e.g. chemotaxis or transmigration). In vivo studies using IVM showed Rho-pip-C1 bound to activated neutrophils in a model of vascular inflammation. The pH-sensitive (“switchable”) version termed Rho-NH-C1 validated these findings, showing fluorescent activity only in inflammatory conditions. Conclusions: These results indicate a viable design of fluorescent probes that have the ability to detect inflammatory events by targeting activated neutrophils.-
dc.description.sponsorshipBritish Pharmacological Society; Wilkinson Trust; EPSRC; German Research Foundation.en_US
dc.publisherIvyspring International Publisheren_US
dc.subjectformyl peptide receptorsen_US
dc.subjectsmall-molecule imaging probesen_US
dc.subjectintravital microscopyen_US
dc.titleTargeting of Formyl Peptide Receptor 2 for in vivo imaging of acute vascular inflammationen_US
Appears in Collections:Dept of Life Sciences Research Papers

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