title: Far-red/near-infrared fluorescence light-up probes for specific in vitro and in vivo imaging of a tumour-related protein.
abstract: As lysosomal protein transmembrane 4 beta (LAPTM4B) is an important biomarker for many solid tumours, development of small-molecule fluorescence light-up probes for detection and imaging of LAPTM4B proteins is particularly valuable. In this work, we reported the design and synthesis of a far-red/near-infrared (FR/NIR) fluorescence light-up probe DBT-2EEGIHGHHIISVG, which could specifically visualize LAPTM4B proteins in cancer cells and tumour-bearing live mice. DBT-2EEGIHGHHIISVG was synthesized by the conjugation of two LAPTM4B-binding peptide ligands (EEGIHGHHIISVG) with one environment-sensitive fluorogen, 4,7-di(thiophen-2-yl)-2,1,3-benzothiadiazole (DBT). Owing to the intramolecular charge transfer character of DBT, DBT-2EEGIHGHHIISVG is weakly emissive in aqueous solution, but switches to fluoresce upon LAPTM4B proteins specifically bind to the peptide ligand of the probe, which provide the DBT with hydrophobic microenvironment, greatly reducing its charge transfer effect with water. It is found that DBT-2EEGIHGHHIISVG can achieve targeted imaging of LAPTM4B proteins in HepG2 cancer cells and visualize LAPTM4B protein-expressed tumour tissues of live mice in a selective and high-contrast manner.
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin, 300071, P. R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Zhujiang Hospital of Southern Medical University, Southern Medical University, Guangzhou 510280, P. R. China.
authors.forename: Yongquan
authors.initials: Y
authors.lastname: Hua
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin, 300071, P. R. China.
authors.forename: Yawen
authors.initials: Y
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin, 300071, P. R. China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Fang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin, 300071, P. R. China.
authors.forename: Shenglu
authors.initials: S
authors.lastname: Ji
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin, 300071, P. R. China.
authors.forename: Zhimou
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Cardiology, Zhujiang Hospital of Southern Medical University, Southern Medical University, Guangzhou 510280, P. R. China.
authors.forename: Caiwen
authors.initials: C
authors.lastname: Ou
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin, 300071, P. R. China.
authors.forename: Deling
authors.initials: D
authors.lastname: Kong
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin, 300071, P. R. China.
authors.forename: Dan
authors.initials: D
authors.lastname: Ding
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D005456:Fluorescent Dyes / Q000737:chemistry*; D056945:Hep G2 Cells; D006801:Humans; D007259:Infrared Rays; D008024:Ligands; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018613:Microscopy, Confocal; D009369:Neoplasms / Q000000981:diagnostic imaging*; D015513:Oncogene Proteins / Q000737:chemistry / Q000378:metabolism*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D011485:Protein Binding; D019265:Spectroscopy, Near-Infrared; D013830:Thiadiazoles / Q000737:chemistry; D014183:Transplantation, Heterologous
chemical_list: D005456:Fluorescent Dyes; C477083:LAPTM4B protein, human; D008024:Ligands; D008565:Membrane Proteins; D015513:Oncogene Proteins; D010455:Peptides; D013830:Thiadiazoles; C015700:benzo-1,2,3-thiadiazole