Chapter 4 Active Targeting of Perfluorocarbon Nanoemulsions

Temme, Sebastian; Grapentin, Christoph; Güden-Silber, Tuba; Flögel, Ulrich

doi:10.1201/9781315364605-5

Cited by 2 publications

(2 citation statements)

References 113 publications

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“…To generate 19 F-based MRI probes, we made use of emulsified, biochemically inert perfluorocarbons (PFCs), which are characterized by a very high payload of 19 F. After intravenous injection, 'neat' PFCs are readily taken up by phagocytic immune cells, which has already been reported as a side effect during their clinical exploration as an artificial blood substitute 8 . Although neutrophils can also be labeled to a certain degree by conventional PFCs as bystander cells, highly specific visualization of this cell type requires active targeting 9,10 of 19 F tracers. Here, we raise this approach to a new level and introduce specific and multimodal PFC targeting for systemic and non-invasive 3D mapping of neutrophil dynamics by combined in vivo 1 H/ 19 F MRI with subsequent ex vivo validation by flow cytometry and fluorescence microscopy.…”

Section: Conjugation Is Required For Specific Uptake Of Mnpmentioning

confidence: 99%

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Non-invasive mapping of systemic neutrophil dynamics upon cardiovascular injury

et al. 2023

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Neutrophils play a complex role during onset of tissue injury and subsequent resolution and healing. To assess neutrophil dynamics upon cardiovascular injury, here we develop a non-invasive, background-free approach for specific mapping of neutrophil dynamics by whole-body magnetic resonance imaging using targeted multimodal fluorine-loaded nanotracers engineered with binding peptides specifically directed against murine or human neutrophils. Intravenous tracer application before injury allowed non-invasive three-dimensional visualization of neutrophils within their different hematopoietic niches over the entire body and subsequent monitoring of their egress into affected tissues. Stimulated murine and human neutrophils exhibited enhanced labeling due to upregulation of their target receptors, which could be exploited as an in vivo readout for their activation state in both sterile and nonsterile cardiovascular inflammation. This non-invasive approach will allow us to identify hidden origins of bacterial or sterile inflammation in patients and also to unravel cardiovascular disease states on the verge of severe aggravation due to enhanced neutrophil infiltration or activation.

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Section: Conjugation Is Required For Specific Uptake Of Mnpmentioning

confidence: 99%

“…9 Clinic for Cardiac Surgery, University Hospital Düsseldorf, Düsseldorf, Germany. 10 Cardiovascular Research Institute Düsseldorf (CARID), Heinrich Heine University, Düsseldorf, Germany. 11 Institute for Translational Pharmacology, Heinrich Heine University, Düsseldorf, Germany.…”

Section: Reporting Summarymentioning

confidence: 99%

Non-invasive mapping of systemic neutrophil dynamics upon cardiovascular injury

et al. 2023

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MRI-based molecular imaging of epicardium-derived stromal cells (EpiSC) by peptide-mediated active targeting

Straub¹,

Nave²,

Bouvain³

et al. 2020

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After myocardial infarction (MI), epicardial cells reactivate their embryonic program, proliferate and migrate into the damaged tissue to differentiate into fibroblasts, endothelial cells and, if adequately stimulated, to cardiomyocytes. Targeting epicardium-derived stromal cells (EpiSC) by specific ligands might enable the direct imaging of EpiSCs after MI to better understand their biology, but also may permit the cell-specific delivery of small molecules to improve the post-MI healing process. Therefore, the aim of this study was to identify specific peptides by phage display screening to enable EpiSC specific cargo delivery by active targeting. To this end, we utilized a sequential panning of a phage library on cultured rat EpiSCs and then subtracted phage that nonspecifically bound blood immune cells. EpiSC specific phage were analyzed by deep sequencing and bioinformatics analysis to identify a total of 78 300 ± 31 900 different, EpiSC-specific, peptide insertion sequences. Flow cytometry of the five most highly abundant peptides (EP1, -2, –3, -7 or EP9) showed strong binding to EpiSCs but not to blood immune cells. The best binding properties were found for EP9 which was further studied by surface plasmon resonance (SPR). SPR revealed rapid and stable association of EpiSCs with EP9. As a negative control, THP-1 monocytes did not associate with EP9. Coupling of EP9 to perfluorocarbon nanoemulsions (PFCs) resulted in the efficient delivery of 19F cargo to EpiSCs and enabled their visualization by 19F MRI. Moreover, active targeting of EpiSCs by EP9-labelled PFCs was able to outcompete the strong phagocytic uptake of PFCs by circulating monocytes. In summary, we have identified a 7-mer peptide, (EP9) that binds to EpiSCs with high affinity and specificity. This peptide can be used to deliver small molecule cargos such as contrast agents to permit future in vivo tracking of EpiSCs by molecular imaging and to transfer small pharmaceutical molecules to modulate the biological activity of EpiSCs.

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Chapter 4 Active Targeting of Perfluorocarbon Nanoemulsions

Cited by 2 publications

References 113 publications

Non-invasive mapping of systemic neutrophil dynamics upon cardiovascular injury

Non-invasive mapping of systemic neutrophil dynamics upon cardiovascular injury

MRI-based molecular imaging of epicardium-derived stromal cells (EpiSC) by peptide-mediated active targeting

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