title: In vivo imaging of β-galactosidase stimulated activity in hepatocellular carcinoma using ligand-targeted fluorescent probe.
abstract: Development of targeted, selective, and noninvasive fluorescent probes for in vivo visualization of tumor-associated overexpressed enzymes are highly anticipated for cancer diagnosis and therapy. Herein, we developed a noninvasive fluorescent probe (DCDHF-βgal) for the sensitive detection, and in vivo visualization of β-galactosidase in hepatocyte HepG2 cells and its xenograft model. As a model system for in vivo targeted imaging, DCDHF-βgal possessing galactose unit selectively target hepatocyte and monitor the β-galactosidase activity with deep tissue penetration, and low background interference. DCDHF-βgal was activated by intracellular β-galactosidases as the driving force for the release of NIR fluorophore, thereby exhibiting ratiometric optical response. Initial fluorescence emission measured at 615 nm was changed to fluorescence at 665 nm upon activation of DCDHF-βgal with β-galactosidase. Ratiometric fluorescence detection of β-galactosidase was also observed in hepatocellular carcinoma cells and tumor xenograft. The noninvasive in vivo optical imaging facilitated by targeted and enzyme-activated imaging agent would be useful in various biomedical and diagnostic applications.
authors.affiliation: Bioimaging Research Team, Korea Basic Science Institute, Cheongju 28119, South Korea.
authors.forename: Eun-Joong
authors.initials: EJ
authors.lastname: Kim
authors.affiliation: Department of Chemistry, Korea University, Seoul 02841, South Korea.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Department of Chemistry, Korea University, Seoul 02841, South Korea.
authors.forename: Amit
authors.initials: A
authors.lastname: Sharma
authors.affiliation: Department of Chemistry, Korea University, Seoul 02841, South Korea.
authors.forename: Byungkwon
authors.initials: B
authors.lastname: Yoon
authors.affiliation: Bioimaging Research Team, Korea Basic Science Institute, Cheongju 28119, South Korea; Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, South Korea.
authors.forename: Hyun Min
authors.initials: HM
authors.lastname: Kim
authors.affiliation: Bioimaging Research Team, Korea Basic Science Institute, Cheongju 28119, South Korea; Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, South Korea.
authors.forename: Hyunseung
authors.initials: H
authors.lastname: Lee
authors.affiliation: Bioimaging Research Team, Korea Basic Science Institute, Cheongju 28119, South Korea; Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, South Korea. Electronic address: kshong@kbsi.re.kr.
authors.forename: Kwan Soo
authors.initials: KS
authors.lastname: Hong
authors.affiliation: Department of Chemistry, Korea University, Seoul 02841, South Korea. Electronic address: jongskim@korea.ac.kr.
authors.forename: Jong Seung
authors.initials: JS
authors.lastname: Kim
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology*; D004789:Enzyme Activation; D005456:Fluorescent Dyes / Q000737:chemistry*; D005690:Galactose / Q000737:chemistry / Q000493:pharmacokinetics*; D056945:Hep G2 Cells; D006801:Humans; D008024:Ligands; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008856:Microscopy, Fluorescence / Q000379:methods*; D057054:Molecular Imaging / Q000379:methods; D015336:Molecular Probe Techniques; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D001616:beta-Galactosidase / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D005456:Fluorescent Dyes; D008024:Ligands; D001616:beta-Galactosidase; D005690:Galactose
keywords: Fluorescent probe; Hepatocellular; In vivo imaging; Ratiometric; β-galactosidase