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DC Field | Value | Language |
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dc.contributor.author | Boltersdorf, T | - |
dc.contributor.author | Ansari, J | - |
dc.contributor.author | Senchenkova, E | - |
dc.contributor.author | Groeper, J | - |
dc.contributor.author | Pajonczyk, D | - |
dc.contributor.author | Vital, S | - |
dc.contributor.author | Kaur, G | - |
dc.contributor.author | Alexander, J | - |
dc.contributor.author | Vogl, T | - |
dc.contributor.author | Rescher, U | - |
dc.contributor.author | Long, N | - |
dc.contributor.author | Gavins, F | - |
dc.date.accessioned | 2020-05-19T10:56:08Z | - |
dc.date.available | 2020-05-19T10:56:08Z | - |
dc.date.issued | 2020-05-17 | - |
dc.identifier.citation | Theranostics, 2020, 10(15): 6599 - 6614 | en_US |
dc.identifier.issn | 1838-7640 | - |
dc.identifier.uri | https://bura.brunel.ac.uk/handle/2438/20851 | - |
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.sponsorship | British Pharmacological Society; Wilkinson Trust; EPSRC; German Research Foundation. | en_US |
dc.language.iso | en | en_US |
dc.publisher | Ivyspring International Publisher | en_US |
dc.subject | Inflammation | en_US |
dc.subject | neutrophils | en_US |
dc.subject | formyl peptide receptors | en_US |
dc.subject | small-molecule imaging probes | en_US |
dc.subject | intravital microscopy | en_US |
dc.title | Targeting of Formyl Peptide Receptor 2 for in vivo imaging of acute vascular inflammation | en_US |
dc.type | Article | en_US |
dc.identifier.doi | https://doi.org/10.7150/thno.44226 | - |
dc.relation.isPartOf | Theranostics | - |
pubs.publication-status | Published | - |
Appears in Collections: | Dept of Life Sciences Research Papers |
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FullText.pdf | 1.79 MB | Adobe PDF | View/Open |
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