Impact of mono- and di-β-galactose moieties in / anticancer efficacy of pyropheophorbide-carbohydrate conjugates by photodynamic therapy.

To investigate the impact of mono- and di-β-galactose moieties in tumor uptake and photodynamic therapy (PDT) efficacy, HPPH [3-(1'-hexyloxy)ethyl-3-devinylpyropheophorobide-a], the meso pyropheophorbide-a [3-ethyl-3-devinyl-pyropheophorbide-a], and the corresponding 20-benzoic acid analogs were used as starting materials. Reaction of the intermediates containing one or two carboxylic acid functionalities with 1-aminogalactose afforded the desired 17- or 20(4')- mono- and 17, 20(4')-di galactose conjugated photosensitizers (PSs) with and without a carboxylic acid group. The overall lipophilicity caused by the presence of galactose in combination with either an ethyl or (1'-hexyloxy)ethyl side chain at position-3 of the macrocycle made a significant difference in uptake by tumor cells and photoreaction upon light exposure. Interestingly, among the PSs investigated, compared to HPPH the carbohydrate conjugates and in which β-galactose moieties are conjugated at positions 17 and 20(4') of meso-pyro pheophorbide-a showed similar efficacy in FaDu cell lines, but in SCID mice bearing FaDu tumors (head & neck) Ps gave significantly improved long-term tumor cure.