title: Imaging of doxorubicin release from theranostic macromolecular prodrugs via fluorescence resonance energy transfer.
abstract: Herein we present a FRET-based theranostic macromolecular prodrug (TMP) composed of (a) dendritic polyglycerol (PG) as polymeric nanocarrier, (b) doxorubicin (Dox) linked via a pH-sensitive hydrazone to (c) a tri-functional linker, and (d) an indodicarbocyanine dye (IDCC) attached in close proximity to Dox. The drug fluorescence is quenched via intramolecular FRET until the pH-sensitive hydrazone bond between the TMP and Dox is cleaved at acidic pH. By measuring its fluorescence, we characterized the TMP cleavage kinetics at different pH values in vitro. The intracellular release of Dox from the carrier was monitored in real time in intact cancer cells, giving more insight into the mode of action of a polymer drug conjugate.
authors.affiliation: Institut für Chemie und Biochemie, Freie Universität Berlin, Takustrasse 3-6, Berlin 14195, Germany.
authors.forename: Harald R
authors.initials: HR
authors.lastname: Krüger
authors.affiliation: Institut für Chemie und Biochemie, Freie Universität Berlin, Takustrasse 3-6, Berlin 14195, Germany; Leibniz-Institut für Molekulare Pharmakologie (FMP) & Freie Universität Berlin, Robert-Roessle-Str. 10, Berlin 13125, Germany.
authors.forename: Irene
authors.initials: I
authors.lastname: Schütz
authors.affiliation: Institut für Chemie und Biochemie, Freie Universität Berlin, Takustrasse 3-6, Berlin 14195, Germany.
authors.forename: Aileen
authors.initials: A
authors.lastname: Justies
authors.affiliation: mivenion GmbH, Robert-Koch-Platz 4, Berlin 10115, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Licha
authors.affiliation: mivenion GmbH, Robert-Koch-Platz 4, Berlin 10115, Germany.
authors.forename: Pia
authors.initials: P
authors.lastname: Welker
authors.affiliation: Institut für Chemie und Biochemie, Freie Universität Berlin, Takustrasse 3-6, Berlin 14195, Germany; Leibniz-Institut für Molekulare Pharmakologie (FMP) & Freie Universität Berlin, Robert-Roessle-Str. 10, Berlin 13125, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Haucke
authors.affiliation: Institut für Chemie und Biochemie, Freie Universität Berlin, Takustrasse 3-6, Berlin 14195, Germany. Electronic address: marcelo.calderon@fu-berlin.de.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Calderón
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry*; D003952:Diagnostic Imaging; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D031541:Fluorescence Resonance Energy Transfer / Q000379:methods*; D005456:Fluorescent Dyes; D005990:Glycerol / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D006835:Hydrazones / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D053758:Nanoparticles; D011108:Polymers / Q000737:chemistry; D011355:Prodrugs / Q000008:administration & dosage* / Q000737:chemistry*
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D005456:Fluorescent Dyes; D006835:Hydrazones; D011108:Polymers; D011355:Prodrugs; C043941:polyglycerol; D004317:Doxorubicin; D005990:Glycerol
keywords: Drug delivery; FRET imaging; Intracellular release; Polymer therapeutic