Tetrahydroporphyrin-tetratosylat (THPTS): A near-infrared photosensitizer for targeted and efficient photodynamic therapy (PDT) of human bladder carcinoma. An in vitro study
Authors
Mandy Berndt-Paetz, Annett Weimann, Nadine Sieger, Stanislaw Schastak,Yasser M. Riyad, Jan Griebel, Vinodh K.A. Arthanareeswaran, Jens-Uwe Stolzenburg,Jochen Neuhaus
Institution
University of Leipzig
Country
Germany
Year
2017
Journal
Photodiagnosis and Photodynamic Therapy
Abstract
tBackground: Efficacy of PDT in muscle-invasive bladder cancer is hampered by low tissue penetrationof most photosensitizers by short excitation wavelength. THPTS is excitable at near-infrared (760 nm)allowing tissue penetration up to 15 mm. We examined the cellular effects of THPTS-PDT in humanbladder cancer cells.Material and methods: We used four human transitional carcinoma cell lines, epithelial bladder pro-genitors (HBLAK) and bladder smooth muscle cells (HBSMC). We used flow cytometry to examinepharmacokinetics of THPTS, confocal laser scanning microscopy to analyze subcellular localization andproduction of reactive oxidative species (ROS), examined cytotoxicity and cell death pathways (qRT-PCR).Results: Total uptake varied between cell lines and was significantly high in HBLAK and HBSMC. Lysosomallocalization was mainly seen in cancer cells and HBLAK, while THPTS was distributed throughout thecytoplasm in HBSMC. Significant ROS production was detected 30 min after THPTS-PDT. Growth arrestoccurred within 4 h and resulted in apoptotic and necrotic cytotoxicity after 24 h. Cytotoxicity was dose-dependent and specifically high in cancer cells and HBLAK and significantly low in HBSMC.Conclusion: THPTS-PDT induces cellular mechanisms leading to cellular growth arrest, apoptosis andnecrosis in human bladder cancer cells. These effects are only partly dependent on the total amount ofTHPTS uptake and rather dependent on its subcellular compartmentalization. HBSMC are hardly affectedby THPTS-PDT confirming tumor specificity and safety. THPTS is a promising new photosensitizer withthe unique advantage of deep tissue penetration allowing the treatment of solid tumors and warrantingfurther animal studies.