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- Title
An Intelligent Nanoplatform for Orthotopic Glioblastoma Therapy by Nonferrous Ferroptosis.
- Authors
Cao, Yue; Zhang, Shuai; Lv, Zhijia; Yin, Na; Zhang, Hao; Song, Peizhe; Zhang, Tianqi; Chen, Yong; Xu, Haiyang; Wang, Yinghui; Liu, Xinrui; Zhao, Gang; Zhang, Hongjie
- Abstract
Ferroptosis, characterized by iron accumulation and lipid peroxidation (LPO), can avoid the intrinsic apoptotic resistance of tumor cells and have been explored for glioblastoma (GBM) therapy. However, the direct delivery of iron species may trigger severe adverse side effects. Using nonferrous species to induce LPO‐mediated ferroptosis maybe a promising strategy for GBM treatment, but there is still no report till now. Therefore, in this study, first an intelligent blood–brain barrier (BBB)‐permeable nanoplatform (PCN‐224@Au/CeO2‐Lf) is constructed for efficient nonferrous ferroptosis‐involved orthotopic GBM therapy. Porous coordination network‐224 nanoparticles (PCN‐224 NPs) are served as sonosensitizers for sonodynamic therapy (SDT). In situ growth of small Au NPs with glucose oxidase (GOx)‐mimic activity and CeO2 NPs with peroxidase (POD)‐ and catalase (CAT)‐mimic abilities are applied for H2O2 self‐supplement, more acidic microenvironment, and generation of cytotoxic hydroxyl radical (·OH) and O2, which improves the efficacy of SDT. Besides, Ce4+‐mediated glutathione (GSH) depletion further promotes ferroptosis and apoptosis. Reactive oxygen species (ROS) burst and GSH consumption‐related glutathione peroxidase 4 (GPX4) deactivation promote the accumulation of LPO, leading to significant nonferrous ferroptosis, which can effectively shrink the orthotopic GBM. These findings first demonstrate the nonferrous ferroptosis strategy for efficient GBM treatment.
- Subjects
GLUCOSE oxidase; GLIOBLASTOMA multiforme; GLUTATHIONE peroxidase; GLUTATHIONE; BLOOD-brain barrier; REACTIVE oxygen species; IRON supplements
- Publication
Advanced Functional Materials, 2022, Vol 32, Issue 51, p1
- ISSN
1616-301X
- Publication type
Article
- DOI
10.1002/adfm.202209227