Glycodendrimeric phenylporphyrins as new candidates for retinoblastoma PDT: Blood carriers and photodynamic activity in cells

Abstract 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 ) (LD 50  = 0.5 μM) in Y79 cells is of the same order of magnitude that for TPP( p -Deg-O-α-ManOH) 3 (LD 50  = 0.7 μM), 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.