title: Targeted luminescent near-infrared polymer-nanoprobes for in vivo imaging of tumor hypoxia.
abstract: Polystyrene nanoparticles (PS-NPs) were doped with an oxygen-sensitive near-infrared (NIR)-emissive palladium meso-tetraphenylporphyrin and an inert reference dye which are both excitable at 635 nm. The nanosensors were characterized with special emphasis on fundamental parameters such as absolute photoluminescence quantum yield and fluorescence lifetime. The PS-NPs were employed for ratiometric dual-wavelength and lifetime-based photoluminescent oxygen sensing. They were efficiently taken up by cultured murine alveolar macrophages, yielding a characteristic and reversible change in ratiometric response with decreasing oxygen concentration. This correlated with the cellular hypoxic status verified by analysis of hypoxia inducible factor-1α (HIF-1α) accumulation. In addition, the surface of PS-NPs was functionalized with polyethylene glycol (PEG) and the monoclonal antibody herceptin, and their binding to HER2/neu-overexpressing tumor cells was confirmed in vitro. First experiments with tumor-bearing mouse revealed a distinctive ratiometric response within the tumor upon hypoxic condition induced by animal sacrifice. These results demonstrate the potential of these referenced NIR nanosensors for in vitro and in vivo imaging that present a new generation of optical probes for oncology.
authors: Department of Hematology and Oncology, University Medical Center Göttingen, Robert-Koch-Strasse 40, 37075 Göttingen, Germany.
authors: Joanna
authors: J
authors: Napp
authors: Thomas
authors: T
authors: Behnke
authors: Lorenz
authors: L
authors: Fischer
authors: Christian
authors: C
authors: Würth
authors: Marieke
authors: M
authors: Wottawa
authors: Dörthe M
authors: DM
authors: Katschinski
authors: Frauke
authors: F
authors: Alves
authors: Ute
authors: U
authors: Resch-Genger
authors: Michael
authors: M
authors: Schäferling
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000737:chemistry / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D000860:Hypoxia; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000737:chemistry; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000175:diagnosis*; D010165:Palladium / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011137:Polystyrenes / Q000737:chemistry*; D011166:Porphyrins / Q000737:chemistry; D011485:Protein Binding; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000737:chemistry / Q000378:metabolism; D019265:Spectroscopy, Near-Infrared; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010165:Palladium; D011092:Polyethylene Glycols; D011137:Polystyrenes; D011166:Porphyrins; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C409084:tetraphenylporphyrin