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.
Bibliographical noteFunding Information:
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.
© 2016, Springer-Verlag Wien.
- Fluorescence imaging
- Matrix metalloproteinase
- Molecular imaging
- Vascular endothelial growth factor receptor