title: Dual-functional, receptor-targeted fluorogenic probe for in vivo imaging of extracellular protease expressions.
abstract: Herein, we report a new type of in vivo fluorogenic probe that enables simultaneous and active targeting of overexpressed receptors, α(V)β(3) integrins, and extracellular proteases, matrix metalloproteinases (MMPs), in the tumor regions. This c(RGDyK)-conjugated MMP fluorogenic probe efficiently targets the tumor regions with high retention time while maintaining receptor binding affinity and substrate activity. The probe minimizes nonspecific accumulation, thus demonstrating improved tumor-to-background signal ratio (T/N) in both α(V)β(3) integrin- and MMP-overexpressing U87MG tumor-bearing mouse model. This strategy can be easily tuned for a wide array of applications targeting various receptors and extracellular proteases in vivo.
authors.affiliation: National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Maryland 20892, United States.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhu
authors.forename: Jin
authors.initials: J
authors.lastname: Xie
authors.forename: Magdalena
authors.initials: M
authors.lastname: Swierczewska
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.forename: Xin
authors.initials: X
authors.lastname: Lin
authors.forename: Xuexun
authors.initials: X
authors.lastname: Fang
authors.forename: Gang
authors.initials: G
authors.lastname: Niu
authors.forename: Seulki
authors.initials: S
authors.lastname: Lee
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D005456:Fluorescent Dyes / Q000032:analysis* / Q000737:chemistry*; D039302:Integrin alphaVbeta3 / Q000737:chemistry / Q000378:metabolism*; D020782:Matrix Metalloproteinases / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D015394:Molecular Structure; D009374:Neoplasms, Experimental / Q000378:metabolism; D010456:Peptides, Cyclic / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D005456:Fluorescent Dyes; D039302:Integrin alphaVbeta3; D010456:Peptides, Cyclic; C507169:cyclic arginine-glycine-aspartic acid peptide; D020782:Matrix Metalloproteinases