title: Biodistribution and photodynamic effects of polyvinylpyrrolidone-hypericin using multicellular spheroids composed of normal human urothelial and T24 transitional cell carcinoma cells.
abstract: Polyvinylpyrrolidone (PVP)-hypericin is a potent photosensitizer that is used in the urological clinic to photodiagnose with high-sensitivity nonmuscle invasive bladder cancer (NMIBC). We examined the differential accumulation and therapeutic effects of PVP-hypericin using spheroids composed of a human urothelial cell carcinoma cell line (T24) and normal human urothelial (NHU) cells. The in vitro biodistribution was assessed using fluorescence image analysis of 5-μm cryostat sections of spheroids that were incubated with PVP-hypericin. The results show that PVP-hypericin accumulated to a much higher extent in T24 spheroids as compared to NHU spheroids, thereby reproducing the clinical situation. Subsequently, spheroids were exposed to different PDT regimes with a light dose ranging from 0.3 to 18 J∕cm2. When using low fluence rates, only minor differences in cell survival were seen between normal and malignant spheroids. High light fluence rates induced a substantial difference in cell survival between the two spheroid types, killing ∼80% of the cells present in the T24 spheroids. It was concluded that further in vivo experiments are required to fully evaluate the potential of PVP-hypericin as a phototherapeutic for NMIBC, focusing on the combination of the compound with methods that enhance the oxygenation of the urothelium.
authors.affiliation: Katholieke Universiteit Leuven, Faculteit Farmaceutische Wetenschappen, Laboratorium voor Farmaceutische Biologie, B-3000 Leuven, Belgium.
authors.forename: Joachim
authors.initials: J
authors.lastname: Vandepitte
authors.forename: Mieke
authors.initials: M
authors.lastname: Roelants
authors.forename: Ben
authors.initials: B
authors.lastname: Van Cleynenbreugel
authors.forename: Klaudia
authors.initials: K
authors.lastname: Hettinger
authors.forename: Evelyne
authors.initials: E
authors.lastname: Lerut
authors.forename: Hendrik
authors.initials: H
authors.lastname: Van Poppel
authors.forename: Peter A M
authors.initials: PA
authors.lastname: de Witte
mesh_terms: D000873:Anthracenes; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D010569:Perylene / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D017319:Photosensitizing Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D011205:Povidone / Q000737:chemistry*; D018874:Spheroids, Cellular / Q000187:drug effects* / Q000473:pathology; D014018:Tissue Distribution; D019459:Urothelium / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology
chemical_list: D000873:Anthracenes; D017319:Photosensitizing Agents; D010569:Perylene; C004965:hypericin; D011205:Povidone