title: Non-invasive optical imaging of matrix metalloproteinase activity with albumin-based fluorogenic nanoprobes during angiogenesis in a mouse hindlimb ischemia model.
abstract: Matrix metalloproteinase (MMP)-2 and MMP-9 have been known to play the role of essential mediators in angiogenesis. Non-invasive in vivo imaging approach using imaging probes is a potential method of detecting MMP activity in living animals, wherein imaging probes must include the characteristics of non-toxicity, specific targetability, and reasonable signal intensity. Here, we developed MMP-specific and self-quenched human serum albumin (HSA)-based (MMP-HSA) nanoprobes for non-invasive optical imaging of MMP activity during angiogenesis in the mouse hindlimb ischemia model. MMP-specific fluorogenic peptide probes, which were self-quenched with a near-infrared fluorophore and a quencher, were covalently conjugated to HSA (MMP-HSA nanoprobes). MMP-HSA nanoprobes formed stable nanoparticle structures of approximately 36 nm in diameter. Strongly self-quenched MMP-HSA nanoprobes boosted intense fluorescence signals in the presence of MMP-2 and MMP-9. Furthermore, MMP-HSA nanoprobes showed no cytotoxicity in cell culture. Importantly, intravenous injection of MMP-HSA nanoprobes provided longer blood half-life and successful non-invasive optical imaging of MMP activity during angiogenesis in the mouse hindlimb ischemia model. In addition, the MMP activity visualized by MMP-HSA nanoprobes was consistent with the results of zymography, Western blot, and immunohistochemistry. MMP-HSA nanoprobes may be useful for monitoring of the initial process of angiogenesis through non-invasive MMP imaging.
authors.affiliation: Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul 136-791, Republic of Korea.
authors.forename: Ju Hee
authors.initials: JH
authors.lastname: Ryu
authors.forename: Jung-Youn
authors.initials: JY
authors.lastname: Shin
authors.forename: Sun Ah
authors.initials: SA
authors.lastname: Kim
authors.forename: Sun-Woong
authors.initials: SW
authors.lastname: Kang
authors.forename: Hyunjoon
authors.initials: H
authors.lastname: Kim
authors.forename: Seokyung
authors.initials: S
authors.lastname: Kang
authors.forename: Kuiwon
authors.initials: K
authors.lastname: Choi
authors.forename: Ick Chan
authors.initials: IC
authors.lastname: Kwon
authors.forename: Byung-Soo
authors.initials: BS
authors.lastname: Kim
authors.forename: Kwangmeyung
authors.initials: K
authors.lastname: Kim
mesh_terms: D000818:Animals; D015153:Blotting, Western; D005260:Female; D006614:Hindlimb / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007511:Ischemia / Q000378:metabolism*; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D051379:Mice; D061848:Optical Imaging / Q000379:methods*; D012709:Serum Albumin / Q000737:chemistry*
chemical_list: D012709:Serum Albumin; D020782:Matrix Metalloproteinases