title: Near-Infrared Fluorogenic Probes with Polarity-Sensitive Emission for in Vivo Imaging of an Ovarian Cancer Biomarker.
abstract: Lysophosphatidic acid (LPA, cutoff values ≥ 1.5 μM) is an effective biomarker for early stage ovarian cancer. The development of selective probes for LPA detection is therefore critical for early clinical diagnosis. Although current methods have been developed for the detection of LPA in solution, they cannot be used for tracking LPA in vivo. Here, we report a near-infrared (NIR) fluorescent probe that can selectively respond to LPA based on polarity-sensitive emission at a very low detection limit of 0.5 μM in situ. This probe exhibits a marked increase of fluorescence at 720 nm upon binding to LPA, allowing the direct visualization of LPA in vitro and in vivo without interference from other biomolecules. Moreover, the probe containing two arginine-glycine-aspartic acid units can be efficiently taken up by cancer cells based on an αvβ3 integrin receptor targeting mechanism. It also exhibits excellent biocompatibility and high pH stability in live cells and in vivo. Confocal laser scanning microscopy and flow cytometric imaging of SKOV-3 cells have confirmed that our probe can be used to image LPA in live cells. In particular, its NIR turn-on fluorescence can be used to effectively monitor LPA imaging in a SKOV-3 tumor-bearing mouse model. Our probe may pave the way for the detection of cancer-related biomarkers and even for early stage cancer diagnosis.
authors.affiliation: Key Laboratory for Advanced Materials & Institute of Fine Chemicals, East China University of Science and Technology , Shanghai 200237, China.
authors.forename: Defan
authors.initials: D
authors.lastname: Yao
authors.affiliation: College of Chemistry and Molecular Engineering, Peking University , Beijing 100871, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Key Laboratory for Advanced Materials & Institute of Fine Chemicals, East China University of Science and Technology , Shanghai 200237, China.
authors.forename: Junchen
authors.initials: J
authors.lastname: Wu
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000737:chemistry; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005456:Fluorescent Dyes / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D008246:Lysophospholipids / Q000032:analysis* / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D009842:Oligopeptides / Q000737:chemistry; D010051:Ovarian Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D019265:Spectroscopy, Near-Infrared; D014183:Transplantation, Heterologous
chemical_list: D014408:Biomarkers, Tumor; D005456:Fluorescent Dyes; D039302:Integrin alphaVbeta3; D008246:Lysophospholipids; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; C032881:lysophosphatidic acid
keywords: biomarker; lysophosphatidic acid; near-infrared; polarity-sensitive; probe