Albumin tailoring molecular rotation and electrophilicity of a GSH-depleting radiosensitizer for potentiating ferroptosis-mediated radioimmunotherapy

被引：2

作者：

Gao, Mingquan ^{[1
]}

Huang, Xie ^{[1
]}

Wu, Zifei ^{[1
]}

Xiao, Weidong ^{[2
]}

Du, Zaizhi ^{[1
]}

Mo, Banghui ^{[1
]}

Wu, Chuan ^{[3
]}

Xing, Haiyan ^{[2
]}

Wang, Weidong ^{[3
]}

Li, Rong ^{[1
]}

Luo, Shenglin ^{[1
]}

机构：

[1] Third Mil Med Univ, Army Med Univ, Coll Prevent Med, State Key Lab Trauma & Chem Poisoning,Inst Combine, Chongqing 400038, Peoples R China

[2] Third Mil Med Univ, Army Med Univ, Daping Hosp, Dept Pharm, Chongqing 400042, Peoples R China

[3] Univ Elect Sci & Technol China, Sichuan Canc Hosp & Inst, Affiliated Canc Hosp, Dept Radiat Oncol,Radiat Oncol Key Lab Sichuan Pro, Chengdu 610000, Peoples R China

来源：

CHEMICAL ENGINEERING JOURNAL | 2024年 / 495卷

基金：

中国国家自然科学基金;

关键词：

Cyanine dye; Radiosensitizer; Human serum albumin; GSH; Ferroptosis; PACLITAXEL; MECHANISMS; CANCER;

D O I：

10.1016/j.cej.2024.153595

中图分类号：

X [环境科学、安全科学];

学科分类号：

08 ; 0830 ;

摘要：

Radiotherapy (RT) is one of the primary treatments for cancer; however, the clinical benefit remains limited owing to intrinsic and acquired radioresistance. In this study, a biocompatible nanocomposite (8HSA8 NPs) is constructed via the self-assembly of human serum albumin (HSA), a glutathione (GSH)-depleting radiosensitizer (808-NM2), and an immunoadjuvant imiquimod (R837). The molecular rotation of 808-NM2 is restricted and the highest occupied and lowest unoccupied molecular orbital (HOMO -LUMO) energy gap is narrowed, enhancing its electrophilicity, radiosensitization effect, and reactivity toward GSH. R837 is released in an acidic tumor microenvironment, which amplifies the immunogenicity of tumor-associated antigens induced by RT in situ . The results indicate that 8HSA8 NPs effectively sensitize tumor cells to RT and induce robust antitumor immunity, thereby effectively inhibiting tumor growth and lung metastasis. Mechanistically, 8HSA8 NPs promote RTinduced ferroptosis via enhancing reactive oxygen species production, GSH depletion, intracellular Fe 2 + accumulation, and inhibiting the SLC7A11 -GSH -glutathione peroxidase 4 axis. 8HSA8 NPs may also reshape the tumor immune microenvironment by amplifying dendritic cells activation, promoting M1 polarization of macrophages, and enhancing tumor-specific CD8 + T cells infiltration. 8HSA8 NPs may provide a promising strategy to reverse radioresistance by potentiating ferroptosis-mediated RT and antitumor immune responses.

引用

页数：15