In vitro and in vivo studies of new photoluminescent oxygen sensors for non-invasive intravascular pO2 measurements

The concentration of oxygen and its rate of consumption are important factors playing a role in PDT and radiotherapy. One of the methods for measuring the tissular oxygen partial pressure (pO2) is based on the use of luminophores presenting an oxygen-dependent quenching of their phosphorescence. The time-resolved luminescence spectroscopy of palladium (PdTCPP) or ruthenium (RuDPP) porphyrin complexes is used for this purpose. Unfortunately, these porphyrin derivatives are phototoxic and leak rapidly out of the blood vessels, making them unsuitable for measuring tissular and or intravascular pO2. Therefore, this research aimed at developing and testing new biocompatible, non-phototoxic oxygen sensors based on palladium complexes incorporated into oxygen permeable, polysaccharide-based nanoparticles appropriate for noninvasive in situ and in vivo measurements of the pO2. In vitro studies, performed with an optical fiber-based time-resolved spectrophotometer, showed that the incorporation of such pO2 probes in nanovectors reduces their sensitivity to oxygen as well as their photobleaching by less than one order of magnitude. However, in vivo biocompatibility studies performed on the chick's embryo chorioallantoic membrane (CAM) model demonstrated that the luminescence of those oxygen probes tends to be heterogeneously distributed within the vasculature. In addition, these probes induce a 'clumping tendency', resulting in a more or less decreased viability of the embryos.

[1]  J. Hendry,et al.  Radiobiology for the Radiologist , 1979, British Journal of Cancer.

[2]  T. Miki,et al.  Selective occlusion of choroidal neovascularization by photodynamic therapy with a water‐soluble photosensitizer, ATX‐S10 , 1999, Lasers in surgery and medicine.

[3]  Ursula E. Spichiger-Keller,et al.  Novel oxygen sensitive complexes for optical oxygen sensing. , 2007, Talanta.

[4]  H. Bergh,et al.  A new drug-screening procedure for photosensitizing agents used in photodynamic therapy for CNV. , 2001, Investigative ophthalmology & visual science.

[5]  J. Vanderkooi,et al.  An optical method for measurement of dioxygen concentration based upon quenching of phosphorescence. , 1987, The Journal of biological chemistry.

[6]  S. U. Dani,et al.  A model system for testing gene vectors using murine tumor cells on the chorioallantoic membrane of the chick embryo. , 2002, Genetics and molecular research : GMR.

[7]  C. Pournaras,et al.  Light-induced retinal vascular damage by Pd-porphyrin luminescent oxygen probes. , 2005, Investigative ophthalmology & visual science.

[8]  D. Delpy,et al.  Optical oxygen sensor based on phosphorescence lifetime quenching and employing a polymer immobilised metalloporphyrin probe , 2006, Medical and Biological Engineering and Computing.

[9]  A. Curnow,et al.  Spatial measurement of oxygen levels during photodynamic therapy using time-resolved optical spectroscopy. , 1998, Journal of photochemistry and photobiology. B, Biology.

[10]  Ravi Kumar M.N.V. Nano and microparticles as controlled drug delivery devices. , 2000 .

[11]  Sergei A Vinogradov,et al.  Oxyphor R2 and G2: phosphors for measuring oxygen by oxygen-dependent quenching of phosphorescence. , 2002, Analytical biochemistry.

[12]  H Ishikawa,et al.  Tumor angiogenic activity of gynecologic tumor cell lines on the chorioallantoic membrane. , 1988, Gynecologic oncology.

[13]  B. Ross,et al.  Production of singlet oxygen by Ru(dpp(SO3)2)3 incorporated in polyacrylamide PEBBLES , 2003 .

[14]  David F Wilson,et al.  Calibration of oxygen-dependent quenching of the phosphorescence of Pd-meso-tetra (4-carboxyphenyl) porphine: a phosphor with general application for measuring oxygen concentration in biological systems. , 1996, Analytical biochemistry.

[15]  G. Nace The Avian Embryo: Structural and Functional Development , 1961 .

[16]  J. Aylott,et al.  A real-time ratiometric method for the determination of molecular oxygen inside living cells using sol-gel-based spherical optical nanosensors with applications to rat C6 glioma. , 2001, Analytical chemistry.

[17]  P. Vaupel,et al.  Hypoxia and Radiation Response in Human Tumors. , 1996, Seminars in radiation oncology.