Glycodendrimeric phenylporphyrins as new candidates for retinoblastoma PDT: Blood carriers and photodynamic activity in cells
2012
Wang, Ze-Jian | Chauvin, Benoît | Maillard, Philippe | Hammerer, Fabien | Carez, Danièle | Croisy, Alain | Sandré, Catherine | Chollet-Martin, Sylvie | Prognon, Patrice | Paul, Jean-Louis | Blais, Jocelyne | Kasselouri, Athena
Photodynamic therapy (PDT) has recently been proposed as a possible indication in the conservative treatment of hereditary retinoblastoma. In order to create photosensitizers with enhanced targeting ability toward retinoblastoma cells, meso-tetraphenylporphyrins bearing one glycodendrimeric moiety have been synthesized. The binding properties to plasma proteins and photodynamic activity of two monodendrimeric porphyrins bearing three mannose units via monoethylene glycol (1) or diethylene glycol (2) linkers have been compared to that of the non-dendrimeric tri-substituted derivative [TPP(p-Deg-O-α-ManOH)₃]. The dendrimeric structure was found to highly increase the binding affinity to plasma proteins and to modify to some extent plasma distribution. HDL and to a lesser extent LDL have been shown to be the main carriers of dendrimeric and non-dendrimeric compounds. The phototoxicity observed for the two glycodendrimers (1) and (2) (LD₅₀=0.5μM) in Y79 cells is of the same order of magnitude that for TPP(p-Deg-O-α-ManOH)₃ (LD₅₀=0.7μM), with a similar cellular uptake level for (1) and a lower for (2). A serum content increase from 2% to 20% (v/v) in the incubation medium was found to inhibit both cellular uptake and photoactivity of dendrimeric derivatives, whereas those of TPP(p-Deg-O-α-ManOH)₃ remained little affected. Specificities of glycodendrimeric porphyrins, combining a lower cellular uptake together with a higher affinity toward plasma proteins, make these derivatives possible candidates for a vascular targeting PDT.
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