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Brain-Targeting Metal-Organic Framework Nanoplatform Reprogramming Ferroptosis Sensitivity of Glioblastoma

文献类型：期刊论文

作者Wang, Mengzhen2; Lai, Yi1,5; Meng, Hanxue2; Jin, Aojia1,5; Zhang, Ping2; Shen, Yinuo2; Lin, Shutong1,5; Yu, Haijun1,5; Xu, Wujun4; Lehto, Vesa-Pekka4
刊名ACS NANO
出版日期2026-01-27
卷号20期号:3页码:2856-2871
关键词Glioblastoma Ferroptosis Radiotherapy Lipid metabolism Metal-organic framework
ISSN号1936-0851
DOI10.1021/acsnano.5c17966
英文摘要Ferroptosis has emerged as a promising therapeutic approach for the treatment of glioblastoma (GBM). However, the efficacy of ferroptosis is limited by the low expression of acyl-coenzyme A synthetase long-chain family member 4 (ACSL4) in GBM cells, a key enzyme that orchestrates ferroptosis by catalyzing polyunsaturated phospholipid synthesis. Additionally, GBM cells display elevated glutathione (GSH) levels and increased activity of glutathione peroxidase 4 (GPX4), resulting in an antioxidant defense system that suppresses ferroptosis. To overcome these challenges, we designed a metal-organic framework (MOF)-based nanoplatform by coordinating Hf4 + and Fe3 + with a tetrakis(4-carboxyphenyl)porphyrin ligand to enhance ferroptosis. The MOF was loaded with brusatol, a nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor, and surface-modified with a transferrin-tannic acid network to enable blood-brain barrier penetration and active GBM targeting. Upon X-ray irradiation, the high-Z element Hf enhanced radiation deposition, which, in turn, upregulated ACSL4 expression and facilitated phospholipid biosynthesis. Simultaneously, Fe3 + released from nanoparticles (NPs) increases the labile iron pool, triggering the Fenton reaction. Meanwhile, brusatol disrupted the Nrf2-GSH-GPX4 axis, suppressing antioxidant defenses and amplifying lipid peroxidation. Consequently, the nanoplatform synergistically induced ferroptosis, effectively suppressing the growth of orthotopic GBM tumors in vivo. Collectively, the MOF-based nanoplatform emerges as a therapeutic strategy for GBM, wherein ferroptosis and the antitumor immune response are synergistically amplified.
资助项目Shanghai Oriental Talents Program[BJKJ2024046] ; Science and Technology Commission of Shanghai Municipality[23490712700] ; National Natural Science Foundation of China[22174047]
WOS研究方向Chemistry ; Science & Technology - Other Topics ; Materials Science
语种英语
WOS记录号WOS:001661501400001
出版者AMER CHEMICAL SOC
源URL[http://119.78.100.183/handle/2S10ELR8/322637]  
专题国家级研究中心_原创新药研究全国重点实验室
通讯作者Zhang, Wen; Xu, Zhiai
作者单位1.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
2.East China Normal Univ, Sch Chem & Mol Engn, Shanghai 200241, Peoples R China
3.East China Normal Univ, Shanghai Engn Res Ctr Mol Therapeut & New Drug Dev, Shanghai 200062, Peoples R China
4.Univ Eastern Finland, Dept Tech Phys, Kuopio 70211, Finland
5.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Wang, Mengzhen,Lai, Yi,Meng, Hanxue,et al. Brain-Targeting Metal-Organic Framework Nanoplatform Reprogramming Ferroptosis Sensitivity of Glioblastoma[J]. ACS NANO,2026,20(3):2856-2871.
APA Wang, Mengzhen.,Lai, Yi.,Meng, Hanxue.,Jin, Aojia.,Zhang, Ping.,...&Xu, Zhiai.(2026).Brain-Targeting Metal-Organic Framework Nanoplatform Reprogramming Ferroptosis Sensitivity of Glioblastoma.ACS NANO,20(3),2856-2871.
MLA Wang, Mengzhen,et al."Brain-Targeting Metal-Organic Framework Nanoplatform Reprogramming Ferroptosis Sensitivity of Glioblastoma".ACS NANO 20.3(2026):2856-2871.

入库方式： OAI收割

来源：上海药物研究所

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