title: Fluorescence imaging with multifunctional polyglycerol sulfates: novel polymeric near-IR probes targeting inflammation.
abstract: We present a highly selective approach for the targeting of inflammation with a multivalent polymeric probe. Dendritic polyglycerol was employed to synthesize a polyanionic macromolecular conjugate with a near-infrared fluorescent dye related to Indocyanine Green (ICG). On the basis of the dense assembly of sulfate groups which were generated from the polyol core, the resulting polyglycerol sulfate (molecular weight 12 kD with ~70 sulfate groups) targets factors of inflammation (IC(50) of 3-6 nM for inhibition of L-selectin binding) and is specifically transported into inflammatory cells. The in vivo accumulation studied by near-IR fluorescence imaging in an animal model of rheumatoid arthritis demonstrated fast and selective uptake which enabled the differentiation of diseased joints (score 1-3) with a 3.5-fold higher fluorescence level and a signal maximum at 60 min post injection. Localization in tissues using fluorescence histology showed that the conjugates are deposited in the inflammatory infiltrate in the synovial membrane, whereas nonsulfated control was not detected in association with disease. Hence, this type of polymeric imaging probe is an alternative to current bioconjugates and provides future options for targeted imaging and drug delivery.
authors.affiliation: mivenion GmbH, Robert-Koch-Platz 4, 10115 Berlin, Germany. licha@mivenion.com
authors.forename: Kai
authors.initials: K
authors.lastname: Licha
authors.forename: Pia
authors.initials: P
authors.lastname: Welker
authors.forename: Marie
authors.initials: M
authors.lastname: Weinhart
authors.forename: Nicole
authors.initials: N
authors.lastname: Wegner
authors.forename: Sylvia
authors.initials: S
authors.lastname: Kern
authors.forename: Stefanie
authors.initials: S
authors.lastname: Reichert
authors.forename: Ines
authors.initials: I
authors.lastname: Gemeinhardt
authors.forename: Carmen
authors.initials: C
authors.lastname: Weissbach
authors.forename: Bernd
authors.initials: B
authors.lastname: Ebert
authors.forename: Rainer
authors.initials: R
authors.lastname: Haag
authors.forename: Michael
authors.initials: M
authors.lastname: Schirner
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000175:diagnosis*; D002460:Cell Line; D050091:Dendrimers / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry; D005990:Glycerol / Q000737:chemistry; D006801:Humans; D007249:Inflammation / Q000175:diagnosis; D011108:Polymers / Q000737:chemistry; D051381:Rats; D013431:Sulfates / Q000737:chemistry
chemical_list: D050091:Dendrimers; D005456:Fluorescent Dyes; D011108:Polymers; D013431:Sulfates; C043941:polyglycerol; D005990:Glycerol