Targeting of Formyl Peptide Receptor 2 for in vivo imaging of acute vascular inflammation.
Theranostics
; 10(15): 6599-6614, 2020.
Article
em En
| MEDLINE
| ID: mdl-32550892
ABSTRACT
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 internalization 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.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Vasculite
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Receptores de Formil Peptídeo
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Corantes Fluorescentes
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Microscopia Intravital
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Neutrófilos
Tipo de estudo:
Prognostic_studies
Limite:
Adult
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Aged
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Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Theranostics
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Reino Unido