Biodistribution and photodynamic effects of polyvinylpyrrolidone-hypericin using multicellular spheroids composed of normal human urothelial and T24 transitional cell carcinoma cells.

Autor: Joachim Vandepitte, Mieke Roelants, Ben Van Cleynenbreugel, Klaudia Hettinger, Evelyne Lerut, Hendrik Van Poppel, Peter A. M. de Witte
Předmět:
Zdroj: Journal of Biomedical Optics; Jan2011, Vol. 16 Issue 1, p018001-018001-6, 1p
Abstrakt: 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 vitrobiodistribution was assessed using fluorescence image analysis of 5-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 NHU spheroids, thereby reproducing the clinical situation. Subsequently,spheroids were exposed to different PDT regimes with a light dose ranging from 0.3 to 18Jcm2. 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 vivoexperiments 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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index