An in situ self‐assembled peptide derivative for inhibition of glutathione synthesis and selective enhancement of tumor radiotherapy

Autor: Xinyan Gong, Benhang Cui, Paiyun Li, Jie Gao, Yang Gao, Xiaoyao Cai, Hang Wang, Wenxue Zhang, Cuihong Yang
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: iRADIOLOGY, Vol 1, Iss 3, Pp 199-208 (2023)
Druh dokumentu: article
ISSN: 2834-2879
2834-2860
DOI: 10.1002/ird3.31
Popis: 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.
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