In vivo monitoring of angiogenesis in a mouse hindlimb ischemia model using fluorescent peptide-based probes
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Vascular endothelial growth factor receptor (VEGFR) and matrix metalloproteinase (MMP) are up-regulated in ischemic tissue and play pivotal roles in promoting angiogenesis. The purpose of the present study was to evaluate two fluorophore-conjugated peptide probes specific to VEGFR and MMP for dual-targeted in vivo monitoring of angiogenesis in a murine model of hindlimb ischemia. To this end, VEGFR-Probe and MMP-Probe were developed by conjugating distinct near-infrared fluorophores to VEGFR-binding and MMP substrate peptides, respectively. VEGFR-Probe exhibited specific binding to VEGFR on HUVECs, and self-quenched MMP-Probe produced strong fluorescence intensity in the presence of MMPs in vitro. Subsequently, VEGFR-Probe and MMP-Probe were successfully utilized for time course in vivo visualization of VEGFR or MMP, respectively. Simultaneous visualization provided information regarding the spatial distribution of these proteins, including areas of co-localization. This dual-targeted in vivo imaging approach will be useful for understanding the detailed mechanism of angiogenesis and for evaluating therapeutic angiogenesis.
KeywordsVascular endothelial growth factor receptor Matrix metalloproteinase Molecular imaging Angiogenesis Fluorescence imaging
This work was supported by Nano-Convergence Foundation (www.nanotech2020.org) funded by the Ministry of Science, ICT and Future Planning (MSIP, Korea) & the Ministry of Trade, Industry and Energy (MOTIE, KOREA) [project name: Development and Commercialization of Nanoparticle Sensor for Detecting Protease Activity], Development of High Medical Technology Project (HI14C2755) of KHIDI, and the Intramural Research Programs of KIST.
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Conflict of interest
There is no conflict of interest for any of the authors.
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