平衡
化学
GPX4
细胞生物学
细胞内
谷胱甘肽
程序性细胞死亡
活性氧
自噬
氧化还原
生物化学
生物物理学
谷胱甘肽过氧化物酶
生物
细胞凋亡
酶
有机化学
作者
Ting Song,Geng Yang,Hanxi Zhang,Mengyue Li,Wanyi Zhou,Chuan Zheng,Fengming You,Chunhui Wu,Yiyao Liu,Hong Yang
出处
期刊:Nano Today
[Elsevier]
日期:2023-08-01
卷期号:51: 101896-101896
被引量:10
标识
DOI:10.1016/j.nantod.2023.101896
摘要
Ferroptosis is an iron-dependent form of cell death that is also a promising tumor therapeutic modality, however, maintaining redox and iron homeostasis in tumor cells limits the ferroptosis therapeutic effect. Herein, we constructed a GSH-depleting magnetic nanoplatform (D@MOs-P) for enhanced ferroptosis by disruption of redox homeostasis and ferritinophagy-mediated iron disorders. D@MOs-P was constructed by coating disulfide bonds-bridged mesoporous silica shells on magnetic nanoparticles (MNPs) and loaded with dihydroartemisinin (DHA, ROS precursor drug). Upon endocytosis by tumor cells, disulfide bond-mediated glutathione depletion and glutathione peroxidase 4 (GPX4) inactivation will synergize with DHA to disrupt intracellular redox homeostasis. On the other hand, the magnetic hyperthermia generated by D@MOs-P will trigger ferritinophagy to achieve tumor iron dyshomeostasis and enhance ferroptosis. Moreover, the released ferrous ions can activate DHA to produce ROS and further disrupt redox homeostasis. Both in vitro and in vivo results demonstrated that D@MOs-P can significant suppression of tumor growth with minimal side effects through the disturbance of dual homeostasis and the intense ferroptosis of tumor cells. Furthermore, MNPs could also provide excellent T2-weighted MR imaging properties. In this work, magnetic hyperthermia was first proven to trigger autophagy-augmented ferroptosis, and the strategies through multi-pathway intracellular homeostasis disruption described in this article can offer an innovative approach in ferroptosis-based antitumor.
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