title: Gold nanoparticles based molecular beacons for in vitro and in vivo detection of the matriptase expression on tumor.
abstract: Matriptase, a type II transmembrane serine protease, is responsible for the early stage proliferation of a wide range of human cancers. It is highly expressed on the surface of tumor cells, allowing the protease to serve as a biomarker of cancer detection. Hence, in this study, we designed two molecular beacons consisting of a fluorescent dye-peptide conjugate attached to gold nanoparticles (Au NPs) for in vitro and in vivo detection of the matriptase expression on tumor cells. The peptide substrate (GRQSRAGC) for matriptase served as the linker between dye (donor) and Au NP (acceptor). In this configuration, the dye fluorescence was quenched by Au NP under physiological conditions and recovered after selective cleavage of the GRQSRAGC by matriptase. To maximize spectral overlap between dye fluorescence and Au NP absorption and optimize the quenching efficiency mediated by fluorescence resonance energy transfer (FRET), the visible dye (fluorescein) and near-infrared (NIR) dye peptide conjugates were each attached to spherical and rod-shaped Au NP for in vitro and in vivo detection, respectively. Both in vitro cell and in vivo animal studies indicate that these two molecular beacons are sensitive and specific for the detection of matriptase expression in the tumor, thereby paving the way to image the activities of this diagnostic protease in living organisms.
authors.affiliation: Department of Biomedical Engineering, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Dawei
authors.initials: D
authors.lastname: Deng
authors.forename: Dongyin
authors.initials: D
authors.lastname: Zhang
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Samuel
authors.initials: S
authors.lastname: Achilefu
authors.forename: Yueqing
authors.initials: Y
authors.lastname: Gu
mesh_terms: D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D005456:Fluorescent Dyes / Q000737:chemistry*; D006046:Gold / Q000737:chemistry*; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009369:Neoplasms / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D012697:Serine Endopeptidases / Q000032:analysis* / Q000378:metabolism
chemical_list: D005456:Fluorescent Dyes; D010455:Peptides; D006046:Gold; D012697:Serine Endopeptidases; C485596:ST14 protein, human
keywords: Gold nanoparticle; In vitro and in vivo detection; Matriptase; Molecular beacon; Peptide substrate