Two New "Protected" Oxyphors for Biological Oximetry: Properties and Application in Tumor Imaging

被引:197
作者
Esipova, Tatiana V. [1 ]
Karagodov, Alexander [1 ]
Miller, Joann [2 ]
Wilson, David F. [1 ]
Busch, Theresa M. [2 ]
Vinogradov, Sergei A. [1 ]
机构
[1] Univ Penn, Dept Biochem & Biophys, Philadelphia, PA 19104 USA
[2] Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA
关键词
OXYGEN SENSORS; PHOSPHORESCENT PROBES; OPTICAL-PROPERTIES; MOLECULAR-OXYGEN; PARTIAL-PRESSURE; LIVING CELLS; BLOOD-FLOW; LUMINESCENCE; FLUORESCENCE; COMPLEXES;
D O I
10.1021/ac2022234
中图分类号
O65 [分析化学];
学科分类号
070302 ; 081704 ;
摘要
We report the synthesis, calibration, and examples of application of two new phosphorescent probes, Oxyphor R4 and Oxyphor G4, optimized specifically for in vivo oxygen imaging by phosphorescence quenching. These "protected" dendritic probes can operate in either albumin-rich (blood plasma) or albumin-free (interstitial space) environments at all physiological oxygen concentrations, from norroxic to deep hypoxic conditions. Oxyphors R4 and G4 are derived from phosphorescent Pd-meso-tetra-(3,5-dicarboxyphenyl)-porphyrin. (PdP) or Pd-meso-tetra-(3,5-dicarboxyphenyl)-tetrabenzoporphyrin (PdTBP), respectively, and possess features common for protected dendritic probes, i.e., hydrophobic dendritic encapsulation of phosphorescent metalloporphyrins and hydrophilic PEGylated periphery. The new Oxyphors are highly soluble in aqueous environments and do not permeate biological membranes. The probes were calibrated under physiological conditions (pH 6.4-7.8) and temperatures (22-38 degrees C), showing high stability, reproducibility of signals, and lack of interactions with biological solutes. Oxyphor G4 was used to dynamically image intravascular and interstitial oxygenation in murine tumors in vivo. The physiological relevance of the measurements was demonstrated by dynamically recording changes in tissue oxygenation during application of anesthesia (isofluorane). These experiments revealed that changes in isofluorane concentration significantly affect tissue oxygenation.
引用
收藏
页码:8756 / 8765
页数:10
相关论文
共 85 条
[11]  
2
[12]   Intravascular oxygen distribution in subcutaneous 9L tumors and radiation sensitivity [J].
Cerniglia, GJ ;
Wilson, DF ;
Pawlowski, M ;
Vinogradov, S ;
Biaglow, J .
JOURNAL OF APPLIED PHYSIOLOGY, 1997, 82 (06) :1939-1945
[13]   Evaluation of phototoxicity of dendritic porphyrin-based phosphorescent oxygen probes: an in vitro study [J].
Ceroni, Paola ;
Lebedev, Artem Y. ;
Marchi, Enrico ;
Yuan, Min ;
Esipova, Tatiana V. ;
Bergamini, Giacomo ;
Wilson, David F. ;
Busch, Theresa M. ;
Vinogradov, Sergei A. .
PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES, 2011, 10 (06) :1056-1065
[14]   Nanometre-sized molecular oxygen sensors prepared from polymer stabilized phospholipid vesicles [J].
Cheng, ZL ;
Aspinwall, CA .
ANALYST, 2006, 131 (02) :236-243
[15]   Probing intracellular oxygen by quenched phosphorescence lifetimes of nanoparticles containing polyacrylamide-embedded [Ru(dpp(SO3Na)2)3]Cl2 [J].
Coogan, Michael P. ;
Court, Jonathan B. ;
Gray, Victoria L. ;
Hayes, Anthony J. ;
Lloyd, Sion H. ;
Millet, Coralie O. ;
Pope, Simon J. A. ;
Lloyd, David .
PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES, 2010, 9 (01) :103-109
[16]   Ratiometric porphyrin-based layers and nanoparticles for measuring oxygen in biosamples [J].
Cywinski, Piotr J. ;
Moro, Artur J. ;
Stanca, Sarmiza E. ;
Biskup, Christoph ;
Mohr, Gerhard J. .
SENSORS AND ACTUATORS B-CHEMICAL, 2009, 135 (02) :472-477
[17]   Synthesis, characterization, and evaluation of [Ir(ppy)2(vpy)Cl] as a polymer-bound oxygen sensor [J].
DeRosa, MC ;
Mosher, PJ ;
Yap, GPA ;
Focsaneanu, KS ;
Crutchley, RJ ;
Evans, CEB .
INORGANIC CHEMISTRY, 2003, 42 (16) :4864-4872
[18]   Luminescent mononuclear and dinuclear iridium(III) cyclometalated complexes immobilized in a polymeric matrix as solid-state oxygen sensors [J].
Di Marco, G ;
Lanza, M ;
Mamo, A ;
Stefio, I ;
Di Pietro, C ;
Romeo, G ;
Campagna, S .
ANALYTICAL CHEMISTRY, 1998, 70 (23) :5019-5023
[19]   Intracellular oxygen-sensitive phosphorescent probes based on cell-penetrating peptides [J].
Dmitriev, Ruslan I. ;
Zhdanov, Alexander V. ;
Ponomarev, Gelii V. ;
Yashunski, Dmitri V. ;
Papkovsky, Dmitri B. .
ANALYTICAL BIOCHEMISTRY, 2010, 398 (01) :24-33
[20]   Oxyphor R2 and G2: phosphors for measuring oxygen by oxygen-dependent quenching of phosphorescence [J].
Dunphy, I ;
Vinogradov, SA ;
Wilson, DF .
ANALYTICAL BIOCHEMISTRY, 2002, 310 (02) :191-198