Photodynamic performance of amphiphilic chlorin e6 derivatives with appropriate properties: A comparison between different-type liposomes as delivery systems

The polyolamide chlorin e6 derivatives show: •A non-ionic neutral hydrophilic character avoiding electrostatic interactions.•Stereochemical homogeneousness.•Rigid amide linkages between the chlorin and carbohydrate units avoiding division.•Effective preparation due to the simple formation of the amide linkages.•Glycosylated e6 chlorin derivatives in liposomes increase the effectiveness of PDT. Many aspects are currently being investigated, with the aim of improving the application of PDT in the clinic by rendering it more effective. One of the current trends focuses on the use of nanocarriers. The aim of this study is to describe novel photosensitizers among polyol amide chlorin e6 derivatives for photodynamic therapy (PDT) using liposomes. In addition to their intracellular localization and antiproliferative activity against HCT116 cells, appropriate photophysical features have been determined (especially high 1O2 quantum yield production). Fluorescent microscopy demonstrated that the compounds entered the endoplasmic reticulum (ER), lysosomes, mitochondria and partially the cytoplasm. All of the chlorins showed no dark cytotoxicity; however, high phototoxicity was observed. Using optical and electron microscopy, we investigated the impact of chlorin-based PDT upon cell damage leading to cell death. Chl ara 3 was identified as the most promising compound among polyol amide chlorin e6 derivatives and improved phototoxicity was observed as compared with a clinically approved temoporfin. Our results indicate that newly-synthesized chlorins seem to be promising candidates for PDT application, and two of them (chl ara 3 and chl mme 2) may create promising new drugs, both in the form of a free compound and as a liposomal formulation.