Photodynamic Efficiency of Diethylene Glycol-Linked Glycoconjugated Porphyrins in Human Retinoblastoma Cells

Photodynamic therapy (PDT) is emerging as a new strategy for the conservative treatment of hereditary retinoblastoma. The glycoconjugated porphyrins TPP(p-Deg-O-α-GalOH)3, TPP(p-Deg-O-β-GalOH)3, TPP(p-Deg-O-α-ManOH)3, and their S-analogues were synthesized to obtain efficient photosensitizers with some retinoblastoma cell affinity. In these systems, a sugar motif and porphyrin core were linked by a diethylene glycol spacer (Deg). Cellular uptake, localization, and photoactivity have been examined in human retinoblastoma cells (Y79). After preincubation with corresponding glycosylated albumin, the uptake of TPP(p-Deg-O-β-GalOH)3 and TPP(p-Deg-O-α-ManOH)3 was 40−45% inhibited, indicating a possible cell-sugar-receptor saturation. High photoactivity was observed for the two α-galacto/manno porphyrins 8 and 10 (LD50 = 0.05 and 0.35 μM, respectively) at 514 nm and low fluence (1 J/cm2). Analysis by MALDI-TOF mass spectrometry only indicated a small metabolic cleavage of the O-glycoconjugates and a good stability of the S-glycoside porphyrins. On the basis of these in vitro data, TPP(p-Deg-O-α-GalOH)3 and TPP(p-Deg-O-α-ManOH)3 were selected for in vivo studies.