Dual‐Modulated Release of a Cytotoxic Photosensitizer Using Photogenerated Reactive Oxygen Species and Glutathione

Autor:	Chae Gyu Lee, Chaiheon Lee, Joonhee Lee, Jung Seung Nam, Byeong‐Su Kim, Tae‐Hyuk Kwon
Rok vydání:	2022
Předmět:	Photosensitizing Agents Polymers Nanogels General Chemistry Disulfides Sulfhydryl Compounds General Medicine Reactive Oxygen Species Glutathione Catalysis
Zdroj:	Angewandte Chemie. 134
ISSN:	1521-3757 0044-8249
DOI:	10.1002/ange.202210623
Popis:	Reversible thiol-disulfide exchange chemistry is of particular interest in drug delivery systems. However, high levels of glutathione (GSH) in cancer cells are hard to distinguish from GSH in normal cells, resulting in unmanageable cytotoxic drug release. This study investigates the spatiotemporally-controlled irreversible degradation of Ir-based photosensitizer (TIr3)-encapsulating nanogels (IrNG) through the hyperoxidation of resulting intracellular thiols using reactive oxygen species (ROS). A highly cytotoxic TIr3 was stably encapsulated within IrNG through hydrophobic interactions and reversible crosslinking between its disulfide bonds and thiols in the absence of light, resulting in high biocompatibility under normal cellular conditions. However, upon photoirradiation, TIr3 generated high levels of ROS, irreversibly oxidizing the thiols to induce electrostatic repulsion between the polymer molecules, resulting in the TIr3 release and induction of cancer cell apoptosis.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7ff60089c2d21bbc74ef0d997cad9f57 https://doi.org/10.1002/ange.202210623 Zobrazit plný text záznamu