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http://bura.brunel.ac.uk/handle/2438/20851
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. |
URI: | https://bura.brunel.ac.uk/handle/2438/20851 |
DOI: | https://doi.org/10.7150/thno.44226 |
ISSN: | 1838-7640 |
Appears in Collections: | Dept of Life Sciences Research Papers |
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