Platinated Porphyrin Tailed with Folic Acid Conjugate for Cell-Targeted Photodynamic Activity

For a precisely targeted photosensitizer, we designed and prepared a new platinated porphyrin (Pt-Por-FA) by Pt-Por tailed with folic acid (FA). The intercalation mode of Pt-Por-FA binding to ct-DNA was confirmed by UV-vis and fluorescent spectra. The singlet oxygen generation of Pt-Por-FA was evaluated through 2', 7'-dichlorofluorescin (DCFH) method. The cellular uptake and the intracellular localization of Pt-Por-FA were studied upon A549 and HeLa cells through confocal laser scanning microscope. The results showed that the red fluorescence of porphyrin conjugate observed in HeLa cells [folate receptor (FR)-positive] was significantly stronger than that of A549 cells (FR-negative), indicating that Pt-Por-FA could target specifically the cancer cells with overexpression of FR via FR-mediated endocytosis. Pt-Por-FA successfully localized in the lysosomes of cancer cells, but Pt-Por without FA did not. Moreover, the cytotoxicity against HeLa and MDA-MB-231 cells was measured by MIT assay. The results demonstrated that Pt-Por-FA had minor cytotoxicity in the dark, but showed a obviously improving toxicity in presence of light. At the concentration of 20 mu M Pt-Por-FA, the cell viabilities were only 12.0% and 26.4% with the IC50, values down to 5 mu m and 12 mu m against HeLa and MDA-MB231 cells, respectively. It suggests that Pt-Por-FA could be a precisely targeted photosensitizer with over-expression of a folate receptor.