title: Mannose-Functionalized Hyperbranched Polyglycerol Loaded with Zinc Porphyrin: Investigation of the Multivalency Effect in Antibacterial Photodynamic Therapy.
abstract: The antibacterial photodynamic activity of hyperbranched polyglycerol (hPG) loaded with zinc porphyrin photosensitizers and mannose units was investigated. hPG, with a MWof 19.5 kDa, was functionalized with about 15 molecules of the photosensitizer {5,10,15-tris(3-hydroxyphenyl)-20-[4-(prop-2-yn-1-ylamino)tetrafluorophenyl]porphyrinato}-zinc(II) by using copper(I)-catalyzed 1,3-dipolar cycloaddition (CuAAC). These nanoparticle conjugates were functionalized systematically with increasing loadings of mannose in the range of approximately 20 to 110 groups. With higher mannose loadings (ca. 58-110 groups) the water-insoluble zinc porphyrin photosensitizer could thus be transferred into a water-soluble form. Targeting of the conjugates was proven in binding studies to the mannose-specific lectin concanavalin A (Con A) by using surface plasmon resonance (SPR). The antibacterial phototoxicity of the conjugates on Staphylococcus aureus (as a typical Gram-positive germ) was investigated in phosphate-buffered saline (PBS). It was shown that conjugates with approximately 70-110 mannose units exhibit significant antibacterial activity, whereas conjugates with approximately 20-60 units did not induce bacterial killing at all. These results give an insight into the multivalency effect in combination with photodynamic therapy (PDT). On addition of serum to the bacterial cultures, a quenching of this antibacterial phototoxicity was observed. In fluorescence studies with the conjugates in the presence of increasing bovine serum albumin (BSA) concentrations, protein-conjugate associations could be identified as a plausible cause for this quenching.
authors.affiliation: Institut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195, Berlin, Germany.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Staegemann
authors.affiliation: Biolitec research GmbH, Otto-Schott-Str. 15, 07745, Jena, Germany.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Gitter
authors.affiliation: Charité-Universitätsmedizin Berlin, Institut für Laboratoriumsmedizin, Klinische Chemie und Pathobiochemie, Campus Virchow Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Dernedde
authors.affiliation: Charité-Universitätsmedizin Berlin, Institut für Laboratoriumsmedizin, Klinische Chemie und Pathobiochemie, Campus Virchow Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Kuehne
authors.affiliation: Institut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195, Berlin, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Haag
authors.affiliation: Institut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195, Berlin, Germany.|Biolitec research GmbH, Otto-Schott-Str. 15, 07745, Jena, Germany.
authors.forename: Arno
authors.initials: A
authors.lastname: Wiehe
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D005990:Glycerol / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008358:Mannose / Q000031:analogs & derivatives*; D008665:Metalloporphyrins / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D053758:Nanoparticles / Q000737:chemistry; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D013203:Staphylococcal Infections / Q000188:drug therapy; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D004337:Drug Carriers; D008665:Metalloporphyrins; D017319:Photosensitizing Agents; D011108:Polymers; C017802:zinc hematoporphyrin; C043941:polyglycerol; D005990:Glycerol; D008358:Mannose
keywords: antibiotics; dendrimers; drug delivery; nanoparticles; porphyrinoids