Abstract
Background: Inhibition of glutathione (GSH) synthesis in cancer cells considerably improves the efficacy of reactive oxygen species (ROS)-related tumor therapy. Self-assembled peptide derivatives can facilitate the efficient delivery and accumulation of small molecular drugs in cancer cells. Methods: Self-assembling modules were covalently linked to the GSH-biosynthesis inhibitor l-buthionine sulfoximine (BSO) by solid-phase synthesis to form the self-assembling peptide derivative Nap-DFDFpY-GG-BSO (Nano-BSO@ in situ). Subsequently, its enzyme-instructed self-assembly in vitro and on cell surfaces were confirmed, and its intracellular GSH depletion and radiotherapy-sensitizing effects were determined. Results: Nano-BSO@ in situ successfully self-assembles into a hydrogel with a nanofibrous microstructure upon incubation with alkaline phosphatase (ALP) at a critical concentration of 9.84 μM. Furthermore, it selectively self-assembles in situ on HeLa cells with high ALP expression. At a concentration of 50 μM, Nano-BSO@ in situ decreases intracellular GSH levels by 80%, ∼2.3 times more than free BSO. Meanwhile, pretreatment of HeLa cells with 50 μM Nano-BSO@ in situ for 24 h results in a radiotherapy sensitization enhancement ratio to γ-rays of 2.09. Conclusions: A novel in situ self-assembling peptide derivative for GSH depletion and selective enhancement of tumor radiotherapy was constructed. The excellent GSH-depletion ability and remarkable radiotherapy-enhancement performance indicate that Nano-BSO@ in situ is a promising selective sensitizer for ROS-related treatment of tumor cells with high ALP expression.
Original language | English |
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Pages (from-to) | 199-208 |
Number of pages | 10 |
Journal | iRADIOLOGY |
Volume | 1 |
Issue number | 3 |
DOIs | |
Publication status | Published - Sept-2023 |
Keywords
- GSH depletion
- in situ self-assembly
- peptide
- radiotherapy