Synchronous Disintegration of Ferroptosis Defense Axis via Engineered Exosome-Conjugated Magnetic Nanoparticles for Glioblastoma Therapy.
Synchronous Disintegration of Ferroptosis Defense Axis via Engineered Exosome-Conjugated Magnetic Nanoparticles for Glioblastoma Therapy.
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通过工程外泌体同步崩解铁死亡防御轴 - 共轭磁性纳米颗粒用于胶质母细胞瘤治疗
DOI：
10.1002/advs.202105451
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发表时间：
2022-06
期刊：
影响因子：
15.1
通讯作者：
Li, Gang
中科院分区：
文献类型：
--
作者：
Li, Boyan;Chen, Xin;Qiu, Wei;Zhao, Rongrong;Duan, Jiazhi;Zhang, Shouji;Pan, Ziwen;Zhao, Shulin;Guo, Qindong;Qi, Yanhua;Wang, Wenhan;Deng, Lin;Ni, Shilei;Sang, Yuanhua;Xue, Hao;Liu, Hong;Li, Gang
胶质母细胞瘤(GBM)是最致命的中枢神经系统肿瘤之一，缺乏有效或足够的治疗方法。铁性下垂是一种新发现的程序性细胞死亡方法，为GBM的治疗开辟了新的方向。然而，血脑屏障(BBB)穿透性差，肿瘤靶向性降低，以及潜在的代偿机制阻碍了铁下垂药物在GBM治疗中的有效性。本文介绍了一种新型的复合治疗平台，该平台结合了磁性纳米颗粒的磁靶向特性和药物释放特性，以及工程外切体的血脑屏障穿透能力和siRNA包埋特性，用于GBM的治疗。这个平台可以在局部磁定位下在大脑中得到丰富，Angiopep-2多肽修饰的工程化外切体可以触发跨细胞作用，允许颗粒通过BBB并通过识别LRP-1受体靶向GBM细胞。通过二氢罗酸脱氢酶的裂解和谷胱甘肽过氧化物酶4铁下垂防御轴与Fe3O4纳米颗粒介导的Fe2+释放的联合作用，实现了对GBM铁下垂的协同治疗。因此，目前的研究结果表明，该系统可以作为治疗胶质母细胞瘤的一个有前途的平台。提出了一种新型的复合治疗平台，该平台将磁性纳米颗粒的磁靶向特性和药物输送特性与工程外切体的血脑屏障穿透能力和siRNA包埋特性相结合，用于治疗胶质母细胞瘤。铁下垂的协同治疗是通过铁下垂防御轴的解体和Fe3O4纳米颗粒介导的Fe2+释放的联合作用而实现的。
Glioblastoma (GBM) is one of the most fatal central nervous system tumors and lacks effective or sufficient therapies. Ferroptosis is a newly discovered method of programmed cell death and opens a new direction for GBM treatment. However, poor blood–brain barrier (BBB) penetration, reduced tumor targeting ability, and potential compensatory mechanisms hinder the effectiveness of ferroptosis agents during GBM treatment. Here, a novel composite therapeutic platform combining the magnetic targeting features and drug delivery properties of magnetic nanoparticles with the BBB penetration abilities and siRNA encapsulation properties of engineered exosomes for GBM therapy is presented. This platform can be enriched in the brain under local magnetic localization and angiopep‐2 peptide‐modified engineered exosomes can trigger transcytosis, allowing the particles to cross the BBB and target GBM cells by recognizing the LRP‐1 receptor. Synergistic ferroptosis therapy of GBM is achieved by the combined triple actions of the disintegration of dihydroorotate dehydrogenase and the glutathione peroxidase 4 ferroptosis defense axis with Fe3O4 nanoparticle‐mediated Fe2+ release. Thus, the present findings show that this system can serve as a promising platform for the treatment of glioblastoma. A novel composite therapeutic platform combining the magnetic targeting features and drug delivery properties of magnetic nanoparticles with the blood–brain barrier penetration abilities and siRNA encapsulation properties of engineered exosomes for Glioblastoma therapy is presented. Synergistic ferroptosis therapy is achieved by the combined actions of the disintegration of ferroptosis defense axis with Fe3O4 nanoparticle‐mediated Fe2+ release.
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影响因子：
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通讯作者：
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影响因子：
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