Nanophotosensitizers for Folate Receptor-Targeted and Redox-Sensitive Delivery of Chlorin E6 against Cancer Cells.

In this study, FA-PEG-ss-Ce6tri copolymer was synthesized to deliver photosensitizers via redox-sensitive and folate receptor-specific manner. Folic acid (FA) was attached to amine end of poly (ethylene glycol) (PEG) (FA-PEG conjugates) and cystamine-conjugated chlorin e6 (Ce6) (Ce6-cystamine conjugates). FA-PEG was further conjugated with Ce6-cystamine to produce FA-PEG-ss-Ce6 conjugates. To the remaining amine end group of Ce6-cystamine conjugates, Ce6 was attached to produce FA-PEG-ss-Ce6tri. Nanophotosensitizers of FA-PEG-ss-Ce6tri copolymer were smaller than 200 nm. Their shapes were disintegrated by treatment with GSH and then Ce6 released by GSH-dependent manner. Compared to Ce6 alone, FA-PEG-ss-Ce6tri copolymer nanophotosensitizers recorded higher Ce6 uptake ratio, reactive oxygen species (ROS) production and cellular cytotoxicity against KB and YD-38 cells. The in vitro and in vivo study approved that delivery of nanophotosensitizers is achieved by folate receptor-sensitive manner. These results indicated that FA-PEG-ss-Ce6tri copolymer nanophotosensitizers are superior candidate for treatment of oral cancer.