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Title: Targeting of Formyl Peptide Receptor 2 for in vivo imaging of acute vascular inflammation
Authors: Boltersdorf, T
Ansari, J
Senchenkova, E
Groeper, J
Pajonczyk, D
Vital, S
Kaur, G
Alexander, J
Vogl, T
Rescher, U
Long, N
Gavins, F
Keywords: Inflammation;neutrophils;formyl peptide receptors;small-molecule imaging probes;intravital microscopy
Issue Date: 17-May-2020
Publisher: Ivyspring International Publisher
Citation: Theranostics, 2020, 10(15): 6599 - 6614
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.
ISSN: 1838-7640
Appears in Collections:Dept of Life Sciences Research Papers

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