Photodynamic efficiency of hypericin compared with chlorin and hematoporphyrin derivatives in HEp-2 and Vero epithelial cell lines

• Photogem, Photodithazine and hypericin were compared.
• Hypericin is more phototoxic than Photogem and Photogem when they are irradiated at 630 nm.
• Hypericin higher cell uptake correlates with its higher photodynamic efficiency.
• The lipophilicity is an important factor for an efficient target cell accumulation.
• Hypericin is the most efficient and a very promising compound for PDT application.

SummaryHypericin (HY) is a photoactive aromatic dianthraquinone that is considered a potent photodynamic agent. In this study, hypericin and two other photosensitizers, a hematoporphyrin derivative (Photogem®; PG) and a chlorin derivative (Photodithazine®; PZ), were compared in terms of their phototoxicity toward two cell lines, HEp-2 and Vero. The median inhibitory concentration (IC50) of each of the photosensitizers was obtained after a 16.2 J cm−2 dose of irradiation at 630 ± 10 nm. The IC50 values were 0.07 ± 0.01 (HY), 1.0 ± 0.2 (PZ), and 9 ± 1 μg mL−1 (PG) in HEp-2 cells and 0.3 ± 0.1 (HY), 1.6 ± 0.2 (PZ) and 11 ± 1 μg mL−1 (PG) in Vero cells, showing that HY is more phototoxic than the others when irradiated at 630 nm. If these results are analyzed, simultaneously, with the first-order constant for BSA tryptophan photooxidation, obtained by fluorescence decay (λexcitation = 280 nm), which are 11 × 10−3 min−1 ± 1. 10−3 min−1 (HY), 10 × 10−3 min−1 ± 1 × 10−3 min−1 (PZ), and 6 × 10−3 min−1 ± 1 × 10−3 min−1 (PG), it is possible to infer that the photodynamic efficiency alone is not sufficient to explain the higher HY phototoxicity. The lipophilicity is also an important factor for an efficient target cell accumulation and was assessed for all sensitizers through the octanol–water partition coefficient (log P): 1.20 ± 0.02 (HY), −0.62 ± 0.03 (PZ), and −0.9 ± 0.2 (PG). The higher value for HY correlates well with its observed superior efficiency to promote damage at low concentrations and doses. As HY is used for the long-term treatment of mild depression, it is considered safe for humans. This fact and the present results reinforce the great potential of this photosensitizer to replace porphyrin derivatives, with the advantages that mean it could be used as photosensitizer in clinical photodynamic therapy.