title: Systemic delivery of protein nanocages bearing CTT peptides for enhanced imaging of MMP-2 expression in metastatic tumor models.
abstract: Matrix metalloproteinase 2 (MMP-2) in metastatic cancer tissue, which is associated with a poor prognosis, is a potential target for tumor imaging in vivo. Here, we describe a metastatic cancer cell-targeted protein nanocage. An MMP-2-binding peptide, termed CTT peptide (CTTHWGFTLC), was conjugated to the surface of a naturally occurring heat shock protein nanocage by genetic modification. The engineered protein nanocages showed a binding affinity for MMP-2 and selective uptake in cancer cells that highly expressed MMP-2 in vitro. In near-infrared fluorescence imaging, the nanocages showed specific and significant accumulation in tumor tissue after intravenous injection in vivo. These protein nanocages conjugated with CTT peptide could be potentially applied to a noninvasive near-infrared fluorescence detection method for imaging gelatinase activity in metastatic tumors in vivo.
authors.affiliation: Innovation Center for Medical Redox Navigation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. t-kawano@dem.med.kyushu-u.ac.jp.
authors.forename: Takahito
authors.initials: T
authors.lastname: Kawano
authors.affiliation: Innovation Center for Medical Redox Navigation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. m-murata@dem.med.kyushu-u.ac.jp.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Murata
authors.affiliation: Department of Advanced Medical Initiatives, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. jingshu@dem.med.kyushu-u.ac.jp.
authors.forename: Jing Shu
authors.initials: JS
authors.lastname: Piao
authors.affiliation: Innovation Center for Medical Redox Navigation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. narahara@dem.med.kyushu-u.ac.jp.
authors.forename: Sayoko
authors.initials: S
authors.lastname: Narahara
authors.affiliation: Department of Advanced Medical Initiatives, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. n.hamano@camiku.kyushu-u.ac.jp.
authors.forename: Nobuhito
authors.initials: N
authors.lastname: Hamano
authors.affiliation: Division of Biopharmaceutics and Pharmacokinetics, Department of Biomedical Engineering, National Cerebral and Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan. jrjhkang@ncvc.go.jp.
authors.forename: Jeong-Hun
authors.initials: JH
authors.lastname: Kang
authors.affiliation: Innovation Center for Medical Redox Navigation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. mhashi@dem.med.kyushu-u.ac.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Hashizume
mesh_terms: D000818:Animals; D019073:HT29 Cells; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D058726:Nanoconjugates; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000378:metabolism*; D061848:Optical Imaging; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011485:Protein Binding; D014018:Tissue Distribution
chemical_list: C415426:CTTHWGFTLC peptide; D058726:Nanoconjugates; D010456:Peptides, Cyclic; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2