1 January 2011 Biodistribution and photodynamic effects of polyvinylpyrrolidone-hypericin using multicellular spheroids composed of normal human urothelial and T24 transitional cell carcinoma cells
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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 18J/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.
© (2011) Society of Photo-Optical Instrumentation Engineers (SPIE)
Joachim Vandepitte, Joachim Vandepitte, Mieke Roelants, Mieke Roelants, Ben Van Cleynenbreugel, Ben Van Cleynenbreugel, Klaudia Hettinger, Klaudia Hettinger, Evelyne Lerut, Evelyne Lerut, Hendrik Van Poppel, Hendrik Van Poppel, Peter A. M. de Witte, Peter A. M. de Witte, } "Biodistribution and photodynamic effects of polyvinylpyrrolidone-hypericin using multicellular spheroids composed of normal human urothelial and T24 transitional cell carcinoma cells," Journal of Biomedical Optics 16(1), 018001 (1 January 2011). https://doi.org/10.1117/1.3533316 . Submission:
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