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 tophotodiagnose with high - sensitivity nonmuscle invasive bladder cancer (NMIBC). We examined the differentialaccumulation and therapeutic effects of PVP-hypericin using spheroids composed of a human urothelial cellcarcinoma cell line (T24) and normal human urothelial (NHU) cells. The in vitro biodistribution was assessedusing fluorescence image analysis of 5- μ m 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 NHUspheroids, thereby reproducing the clinical situation. Subsequently , spheroids were exposed to different PDTregimes with a light dose ranging from 0.3 to 18J/cm 2 . When using low fluence rates, only minor differences incell survival were seen between normal and malignant spheroids. High light fluence rates induced a substantialdifference in cell survival between the two spheroid types, killing ∼80% of the cells present in the T24 spheroids.It was concluded that further