Research Papers: Therapeutic

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

[+] Author Affiliations
Joachim Vandepitte, Mieke Roelants, Peter A. M. de Witte

Katholieke Universiteit Leuven, Faculteit Farmaceutische Wetenschappen, Laboratorium voor Farmaceutische Biologie, B-3000 Leuven, Belgium

Ben Van Cleynenbreugel, Hendrik Van Poppel

Katholieke Universiteit Leuven, Faculteit Geneeskunde, Dienst Urologie, B-3000 Leuven, Belgium

Klaudia Hettinger

Sanochemia Pharmazeutika AG, 1090 Vienna, Austria

Evelyne Lerut

Katholieke Universiteit Leuven, Faculteit Geneeskunde, Afdeling Cellulaire Morfologie en Pathologie, B-3000 Leuven, Belgium

J. Biomed. Opt. 16(1), 018001 (January 27, 2011). doi:10.1117/1.3533316
History: Received July 12, 2010; Revised November 17, 2010; Accepted November 18, 2010; Published January 27, 2011; Online January 27, 2011
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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.

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© 2011 Society of Photo-Optical Instrumentation Engineers (SPIE)

Citation

Joachim Vandepitte ; Mieke Roelants ; Ben Van Cleynenbreugel ; Klaudia Hettinger ; Evelyne Lerut, et al.
"Biodistribution and photodynamic effects of polyvinylpyrrolidone-hypericin using multicellular spheroids composed of normal human urothelial and T24 transitional cell carcinoma cells", J. Biomed. Opt. 16(1), 018001 (January 27, 2011). ; http://dx.doi.org/10.1117/1.3533316


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