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

Xinyan Gong, Benhang Cui, Paiyun Li, Jie Gao, Yang Gao, Xiaoyao Cai, Hang Wang, Wenxue Zhang*, Cuihong Yang*

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    2 Citations (Scopus)

    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 languageEnglish
    Pages (from-to)199-208
    Number of pages10
    JournaliRADIOLOGY
    Volume1
    Issue number3
    DOIs
    Publication statusPublished - Sept-2023

    Keywords

    • GSH depletion
    • in situ self-assembly
    • peptide
    • radiotherapy

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