title: Enhancing the photodynamic effect of hypericin in human bladder transitional cell carcinoma spheroids by the use of the oxygen carrier, perfluorodecalin.
abstract: In the present study, we evaluated the possibility of enhancing the photodynamic effect of hypericin in transitional cell carcinoma (TCC) spheroids by the use of the oxygen carrier, perfluorodecalin. Following incubation with hypericin, RT-112 TCC spheroids were irradiated in the presence or absence of perfluorodecalin, at light doses of 7 J/cm(2) or 28 J/cm(2) , delivered at a fluence rate of 15 mW/cm(2) . The photodynamic therapy (PDT) efficacy was evaluated and apoptotic cells were visualized. The results show that, in the absence of perfluorodecalin, spheroidal TCC cells are inadequately sensitive to hypericin PDT. As was shown by fluorescence microscopy, this lack of activity was not due to insufficient photoactive concentrations of hypericin reaching the inner parts of the spheroids. Conversely, enhanced oxygenation of spheroids by perfluorodecalin led to a dramatic enhancement of hypericin PDT efficacy. The detection of nuclear shrinkage or fragmentation with DAPI staining and the assessment of cell morphology by light microscopy indicated that apoptosis was the most prominent response of spheroids to hypericin PDT in the presence of perfluorodecalin. In conclusion, the results of this study suggest that perfluorocarbons, such as perfluorodecalin, are useful in enhancing the oxygenation of tumor tissue, resulting in highly efficient hypericin PDT. Since hypericin becomes concentrated specifically in human bladder urothelial carcinoma lesions and the bladder is very well suited to instillation with a perfluorocarbon, combining the techniques looks very promising for an efficient and selective whole bladder wall photodynamic antitumoral treatment in a urological clinical setting.
authors.affiliation: Laboratorium voor Farmaceutische Biologie en Fytofarmacologie, Faculteit Farmaceutische Wetenschappen, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.
authors.forename: Appolinary R
authors.initials: AR
authors.lastname: Kamuhabwa
authors.forename: Ann
authors.initials: A
authors.lastname: Huygens
authors.forename: Tania
authors.initials: T
authors.lastname: Roskams
authors.forename: Peter A M
authors.initials: PA
authors.lastname: De Witte
mesh_terms: D000873:Anthracenes; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005466:Fluorocarbons / Q000627:therapeutic use*; D006801:Humans; D008027:Light; D008856:Microscopy, Fluorescence; D010100:Oxygen / Q000378:metabolism; D010569:Perylene / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010778:Photochemotherapy / Q000379:methods; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use; D018874:Spheroids, Cellular / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000473:pathology
chemical_list: D000873:Anthracenes; D000970:Antineoplastic Agents; D005466:Fluorocarbons; D011838:Radiation-Sensitizing Agents; C008805:perfluorodecalin; D010569:Perylene; C004965:hypericin; D010100:Oxygen