Transferrin-mediated targeting of hypericin embedded in sterically stabilized PEG-liposomes

Over the last few decades, photodynamic therapy evolved to a promising new treating modality for cancer. The photosensitizers used, induce light sensitivity to a normal light insensitive chemical or physical process. Third generation photosensitizers are derivatives of second generation photosensitizers introduced into or attached to chemical devices. This modification increases the biological specificity to deliver photosensitizers to a defined cell type. The aim of this study was to improve the specificity of hypericin for tumor cells using transferrin-conjugated PEG-liposomes. Transferrin was used as tumor-seeking molecule, since many tumor cells, among which HeLa cells, overexpress transferrin receptors on their surface. Hypericin, a potent second generation photosensitizer, was integrated in the lipid bilayers of the liposomes. The antiproliferative effect of the targeted PEG-liposomes was determined and compared with the results of non-targeted PEG-liposomes and free hypericin. Additionally, the intracellular accumulation assay was performed. All manipulations were done on HeLa cells. To interpret the results, the data were supplemented by findings concerning embedding stability. Targeting hypericin by transferrin-conjugated PEG-liposomes did not significantly favour the photocytotoxicity and the intracellular accumulation of hypericin, in comparison with non-targeted PEG-liposomes or free hypericin. Embedding stability experiments showed only limited stable embedding. Despite of their proven efficiency as a targeting carrier system, transferrin-conjugated PEG-liposomes seem less effective in targeting hypericin to tumor cells due to the amount of hypericin leaking out of the PEG-liposomes.