Design, synthesis and biological evaluation of folate-porphyrin: a new photosensitizer for targeted photodynamic therapy

Abstract

A novel folate-porphyrin conjugate 1 for targeted photodynamic therapy of tumor was designed and synthesized. The results of fluorescence spectroscopy and confocal laser scanning microscope demonstrated that the cellular uptake of conjugate 1 by HeLa cells was 35 times higher than that of precursor porphyrin 3 after 24 h incubation, and that the presence of excessive free folic acid inhibited the cellular uptake of conjugate 1. Cytotoxicity against folate-receptor positive HeLa cells in vitro measured by MTT assay demonstrated that conjugate 1 exhibited much lower dark cytotoxicity but significant photocytotoxicity, with 86.4% of cell growth inhibition ratio after irradiation. However, conjugate 1 induced lower photocytotoxicity for normal cells and folate-receptor negative cells. These results suggest that folate-porphyrin like photosensitizers could induce a potentially useful targeted photodynamic therapy modality for folate-receptor-positive cancer cells due to the folate-receptor mediated endocytosis.