Non-invasive optical imaging of matrix metalloproteinase activity with albumin-based fluorogenic nanoprobes during angiogenesis in a mouse hindlimb ischemia model

作者：Ryu Ju Hee; Shin Jung Youn; Kim Sun Ah; Kang Sun Woong; Kim Hyunjoon; Kang Seokyung; Choi Kuiwon; Kwon Ick Chan; Kim Byung Soo; Kim Kwangmeyung^*

来源：Biomaterials, 2013, 34(28): 6871-6881.

DOI：10.1016/j.biomaterials.2013.05.074

• Matrix metalloproteinase
• Albumin
• Molecular imaging
• Angiogenesis
• Fluorescence

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.

• 出版日期2013-9