Jo, J.; Kim, J.Y.; Yun, J.-J.; Lee, Y.J.; Jeong, Y.-I. β-Cyclodextrin Nanophotosensitizers for Redox-Sensitive Delivery of Chlorin e6. Molecules2023, 28, 7398.
Jo, J.; Kim, J.Y.; Yun, J.-J.; Lee, Y.J.; Jeong, Y.-I. β-Cyclodextrin Nanophotosensitizers for Redox-Sensitive Delivery of Chlorin e6. Molecules 2023, 28, 7398.
Jo, J.; Kim, J.Y.; Yun, J.-J.; Lee, Y.J.; Jeong, Y.-I. β-Cyclodextrin Nanophotosensitizers for Redox-Sensitive Delivery of Chlorin e6. Molecules2023, 28, 7398.
Jo, J.; Kim, J.Y.; Yun, J.-J.; Lee, Y.J.; Jeong, Y.-I. β-Cyclodextrin Nanophotosensitizers for Redox-Sensitive Delivery of Chlorin e6. Molecules 2023, 28, 7398.
Abstract
The aim of this study is to prepare redox-sensitive nanophotosensitizers for targeted delivery of chlorin e6 (Ce6) against cervical cancer. For this purpose, Ce6 was conjugated with β-cyclodextrin (bCD) via disulfide bond creating nanophotosensitizers that were fabricated for redox-sensitive delivery of Ce6 against cancer cells. bCD was treated with succinic anhydride to synthesize suc-cinylated bCD (bCDsu). After that, cystamine was attached to the carboxylic end of bCDsu (bCDsu-ss) and the amine end group of bCDsu-ss was conjugated with Ce6 (bCDsu-ss-Ce6). Chemical composition of bCDsu-ss-Ce6 was confirmed with 1H and 13C NMR spectra. bCDsu-ss-Ce6 nanophotosensitizers were fabricated by dialysis procedure. They formed small particles with an average particle size of 152.0±23.2 nm and they showed improved singlet oxygen (SO) generation in the aqueous solution under light irradiation and was significantly higher than that of Ce6 alone. Ce6 release rate from bCDsu-ss-Ce6 nanophotosensitizers was accelerated by addition of glutathione (GSH), indicating that bCDsu-ss-Ce6 nanophotosensitizers have re-dox-sensitive photosensitizer delivery capacity. bCDsu-ss-Ce6 nanophotosensitizers have low in-trinsic cytotoxicity against CCD986Sk human skin fibroblast cells as well as Ce6 alone. However, bCDsu-ss-Ce6 nanophotosensitizers showed improved Ce6 uptake ratio, higher reactive oxygen species (ROS) production and phototoxicity compared to those of Ce6 alone. GSH addition resulted in higher Ce6 uptake ratio, ROS generation and phototoxicity than those of Ce6 alone, indicating that bCDsu-ss-Ce6 nanophotosensitizers have redox-sensitive biological activity in vitro against HeLa human cervical cancer cells. At tumor xenograft model using HeLa cells, bCDsu-ss-Ce6 nanophotosensitizers efficiently accumulated in the tumor rather than normal organs, i.e. fluores-cence intensity in tumor tissues was significantly higher than those of other organs while Ce6 alone did not specifically target tumor tissue. These results indicated higher anticancer activity of bCDsu-ss-Ce6 nanophotosensitizers, by efficiently inhibiting growth of tumor in in vivo animal tumor xenograft study.
Keywords
β-Cyclodextrin; redox-sensitive; cancer targeting; photodynamic therapy; chlorin e6
Subject
Chemistry and Materials Science, Biomaterials
Copyright:
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