title: Exploiting Fluorescence Lifetime Plasticity in FLIM: Target Molecule Localization in Cells and Tissues.
abstract: The mechanisms of drug-receptor interactions and the controlled delivery of drugs via biodegradable and biocompatible nanoparticulate carriers are active research fields in nanomedicine. Many clinically used drugs target G-protein coupled receptors (GPCRs) due to the fact that signaling via GPCRs is crucial in physiological and pathological processes and thus central for the function of biological systems. In this letter, a fast and reliable ratiometric fluorescence lifetime imaging microscopy (rmFLIM) approach is described to analyze the distribution of protein-ligand complexes in the cellular context. Binding of the fluorescently labeled antagonist naloxone to the G-protein coupled μ-opioid receptor is used as an example. To show the broad applicability of the rmFLIM method, we extended this approach to investigate the distribution of polymer-based nanocarriers in histological liver sections.
authors.affiliation: Institut für Experimentalphysik, Freie Universität Berlin, Arnimallee 14, D-14195 Berlin, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Boreham
authors.affiliation: Institut für Experimentalphysik, Freie Universität Berlin, Arnimallee 14, D-14195 Berlin, Germany.
authors.forename: T-Y
authors.initials: TY
authors.lastname: Kim
authors.affiliation: Klinik für Anästhesiologie, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Spahn
authors.affiliation: Klinik für Anästhesiologie, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Stein
authors.affiliation: Institut für Tierpathologie, Freie Universität Berlin, Robert-von-Ostertag-Strasse 15, 14163 Berlin, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Mundhenk
authors.affiliation: Institut für Tierpathologie, Freie Universität Berlin, Robert-von-Ostertag-Strasse 15, 14163 Berlin, Germany.
authors.forename: A D
authors.initials: AD
authors.lastname: Gruber
authors.affiliation: Institut für Chemie und Biochemie, Freie Universität Berlin, Takustrasse 3, 14195 Berlin, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Haag
authors.affiliation: mivenion GmbH, Robert-Koch-Platz 4, 10115 Berlin, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Welker
authors.affiliation: mivenion GmbH, Robert-Koch-Platz 4, 10115 Berlin, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Licha
authors.affiliation: Institut für Experimentalphysik, Freie Universität Berlin, Arnimallee 14, D-14195 Berlin, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Alexiev
keywords: FLIM; G-protein coupled receptors; ligand binding; nanocarrier; μ-opioid receptor