BibTex format
@article{Boltersdorf:2020:10.7150/thno.44226,
author = {Boltersdorf, T and Ansari, J and Senchenkova, EY and Groeper, J and Pajonczyk, D and Vital, SA and Kaur, G and Alexander, JS and Vogl, T and Rescher, U and Long, NJ and Gavins, FNE},
doi = {10.7150/thno.44226},
journal = {Theranostics},
pages = {6599--6614},
title = {Targeting of formyl peptide receptor 2 for in vivo imaging of acute vascular inflammation},
url = {http://dx.doi.org/10.7150/thno.44226},
volume = {10},
year = {2020}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - 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.
AU - Boltersdorf,T
AU - Ansari,J
AU - Senchenkova,EY
AU - Groeper,J
AU - Pajonczyk,D
AU - Vital,SA
AU - Kaur,G
AU - Alexander,JS
AU - Vogl,T
AU - Rescher,U
AU - Long,NJ
AU - Gavins,FNE
DO - 10.7150/thno.44226
EP - 6614
PY - 2020///
SN - 1838-7640
SP - 6599
TI - Targeting of formyl peptide receptor 2 for in vivo imaging of acute vascular inflammation
T2 - Theranostics
UR - http://dx.doi.org/10.7150/thno.44226
UR - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000534614200003&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR - https://www.thno.org/v10p6599.htm
UR - http://hdl.handle.net/10044/1/80213
VL - 10
ER -
