title: High-affinity peptide against MT1-MMP for in vivo tumor imaging.
abstract: Membrane type-1 matrix metalloproteinase (MT1-MMP) is a key member of the matrix metalloproteinase (MMP) family. It participates in pericellular proteolysis of extracellular matrix (ECM) macromolecules and is essential for many biological and pathological processes, such as tumor development, angiogenesis and metastasis. A ligand that specifically binds to MT1-MMP may facilitate the labeling of this molecule, allow imaging at the cellular and organism levels, and provide a means for targeted drug delivery specific to MT1-MMP. A non-substrate MT1-MMP binding peptide was identified by screening a Ph.D.-12™ phage display peptide library and conjugated with near-infrared fluorescent (NIRF) dye Cy5.5 for tumor imaging. Peptide HWKHLHNTKTFL (denoted as MT1-AF7p) showed high MT1-MMP binding affinity. Computer modeling verified that MT1-AF7p binds to the MT-loop region of MT1-MMP and interacts with MT1-MMP through hydrogen bonding and hydrophobic interactions. MDA-MB-435 xenografts with high MT1-MMP expression had significantly higher tumor accumulation and better tumor contrast than the low MT1-MMP expressing A549 xenografts after intravenous injection of Cy5.5-MT1-AF7p. Using NIRF imaging, we have demonstrated specific targeting of MT1-AF7p to MT1-MMP-expressing tumors. Thus, MT1-AF7p is an important tool for noninvasive monitoring of MT1-MMP expression in tumors, and it shows great potential as an imaging agent for MT1-MMP-positive tumors.
authors.affiliation: Key Laboratory of Molecular Enzymology and Enzyme Engineering of the Ministry of Education, Jilin University, Changchun 130023, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhu
authors.forename: Huiling
authors.initials: H
authors.lastname: Wang
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Ye
authors.initials: Y
authors.lastname: Wang
authors.forename: Kun
authors.initials: K
authors.lastname: Jiang
authors.forename: Cheng
authors.initials: C
authors.lastname: Li
authors.forename: Qingjie
authors.initials: Q
authors.lastname: Ma
authors.forename: Shi
authors.initials: S
authors.lastname: Gao
authors.forename: Liping
authors.initials: L
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Mingjun
authors.initials: M
authors.lastname: Cai
authors.forename: Hongda
authors.initials: H
authors.lastname: Wang
authors.forename: Gang
authors.initials: G
authors.lastname: Niu
authors.forename: Seulki
authors.initials: S
authors.lastname: Lee
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.forename: Xuexun
authors.initials: X
authors.lastname: Fang
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Chen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002232:Carbocyanines / Q000032:analysis / Q000737:chemistry*; D002417:Cattle; D045744:Cell Line, Tumor; D006801:Humans; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D051598:Whole Body Imaging / Q000379:methods*
chemical_list: C098793:CY5.5 cyanine dye; D002232:Carbocyanines; D019151:Peptide Library; D010455:Peptides; D053511:Matrix Metalloproteinase 14