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8 February 2008 Intracellular uptake and intraspheroidal distribution of hypericin and hydrophilic analogues using E-cadherin transfected T-24 human bladder cancer cells
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Abstract
Hypericin (HYP) is used after instillation as a diagnostic tool for the fluorescence detection of CIS in the human bladder. In this study the in vitro cellular accumulation and intraspheroidal distribution of HYP and three analogues (OH1, OH2, OH3) with gradually increasing hydrophilicity were studied. E-cadherin negative (T24-C1-) and E-cadherin positive (T24-H3++) human bladder cancer cells were used. We report that in the presence of FBS all compounds were taken up by the monolayer cells to the same limited extent, whereas the overall intracellular accumulation was substantially higher when the incubation of the different dyes took place using cell medium not supplemented with FBS. The results of this study therefore confirm the competition between cellular uptake of HYP and analogues and binding to FBS constituents. Investigating the permeation of the compounds in spheroids, it was found that all HYP analogues diffused dramatically better through the three-dimensional cell layers than HYP itself. This enhanced ability of hydrophilic HYP analogues to permeate through the cell layers in the presence of FBS can be explained in terms of a preferred binding to HDL as compared to LDL. The results further show that all compounds, including LDL-binding HYP, substantially permeated better in T24-C1- spheroids than in T24-H3++ spheroids. The data therefore support the hypothesis that a lowered cellular cohesion is the key to understand the selective uptake of hypericin and its analogues in malignant urothelial cells.
© (2008) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.
Ivo Crnolatac, Ann Huygens, and Peter A. M. de Witte "Intracellular uptake and intraspheroidal distribution of hypericin and hydrophilic analogues using E-cadherin transfected T-24 human bladder cancer cells", Proc. SPIE 6842, Photonic Therapeutics and Diagnostics IV, 684219 (8 February 2008); https://doi.org/10.1117/12.763281
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