title: Non-invasive optical imaging of cathepsin B with activatable fluorogenic nanoprobes in various metastatic models.
abstract: An increasing number of treatments of metastases rely on diagnostics and imaging these days. The facts that the activity of cathepsin B (CB) is markedly linked to the metastatic process and that CB is found highly expressed in the pericellular regions in this process make CB an attractive target for diagnosing metastases. We have developed a CB-sensitive nanoprobe (CB-CNP) consisting of self-quenched CB-sensitive fluorogenic peptide probes conjugated onto the surface of tumor-targeting glycol chitosan nanoparticles (CNPs). The freshly prepared CB-CNP formed a spherical nanoparticle structure (280 nm in diameter) and the fluorescence intensity of CB-CNP was strongly quenched in physiological condition. However, self-quenched CB-CNP boosted strong fluorescence signals in the presence of CB, not of cathepsin l or cathepsin d, due to the CB-specific cleavage of self-quenched peptide probes. Importantly, the intravenously injected CB-CNP demonstrated the potential to discriminate metastases in vivo in three metastatic mouse models, including 4T1-luc2 liver metastases, RFP-B16F10 lung metastases and HT1080 peritoneal metastases. Indeed, Western blot analysis confirmed that the CB expression of metastases had increased compared to normal organ in these metastatic mouse models. CB-CNPs may be useful for depicting metastases through non-invasive CB molecular 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; School of Chemical and Biological Engineering, Seoul National University, San 56-1, Sillim-dong, Gwanak-gu, Seoul 151-744, Republic of Korea.
authors.forename: Ju Hee
authors.initials: JH
authors.lastname: Ryu
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: Jin Hee
authors.initials: JH
authors.lastname: Na
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: Ho Kyung
authors.initials: HK
authors.lastname: Ko
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; Departments of Polymer Science and Chemical Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Dong Gil
authors.initials: DG
authors.lastname: You
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; Departments of Polymer Science and Chemical Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Subin
authors.initials: S
authors.lastname: Park
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; Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 700-422, Republic of Korea.
authors.forename: Eunsung
authors.initials: E
authors.lastname: Jun
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; Department of Fundamental Pharmaceutical Sciences, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: Ho Jun
authors.initials: HJ
authors.lastname: Yeom
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; Department of Life and Nanopharmaceutical Science, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: Deok Ho
authors.initials: DH
authors.lastname: Seo
authors.affiliation: Departments of Polymer Science and Chemical Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Jae Hyung
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Fundamental Pharmaceutical Sciences, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea; Department of Life and Nanopharmaceutical Science, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: Seo Young
authors.initials: SY
authors.lastname: Jeong
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; Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 700-422, Republic of Korea.
authors.forename: In-San
authors.initials: IS
authors.lastname: Kim
authors.affiliation: School of Chemical and Biological Engineering, Seoul National University, San 56-1, Sillim-dong, Gwanak-gu, Seoul 151-744, Republic of Korea.
authors.forename: Byung-Soo
authors.initials: BS
authors.lastname: Kim
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; KU-KIST School, Korea University, 1 Anam-dong, Seongbuk-gu, Seoul 136-701, Republic of Korea.
authors.forename: Ick Chan
authors.initials: IC
authors.lastname: Kwon
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. Electronic address: choi@kist.re.kr.
authors.forename: Kuiwon
authors.initials: K
authors.lastname: Choi
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. Electronic address: kim@kist.re.kr.
authors.forename: Kwangmeyung
authors.initials: K
authors.lastname: Kim
mesh_terms: D002401:Cathepsin B / Q000378:metabolism*; D045744:Cell Line, Tumor; D048271:Chitosan / Q000737:chemistry; D003110:Colonic Neoplasms / Q000473:pathology; D005456:Fluorescent Dyes / Q000737:chemistry*; D006801:Humans; D008954:Models, Biological; D049329:Nanostructures; D009362:Neoplasm Metastasis; D061848:Optical Imaging / Q000379:methods*
chemical_list: D005456:Fluorescent Dyes; D048271:Chitosan; D002401:Cathepsin B
keywords: Cathepsin B; Fluorescence; Metastasis; Metastatic mouse model; Molecular imaging