Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA.
Department of Bioengineering, University of Illinois at Chicago, Chicago, IL, 60607, USA.
Nat Commun. 2020 Jul 20;11(1):3637. doi: 10.1038/s41467-020-17380-5.
We report a strategy to boost Fenton reaction triggered by an exogenous circularly polarized magnetic field (MF) to enhance ferroptosis-like cell-death mediated immune response, as well as endow a responsive MRI capability by using a hybrid core-shell vesicles (HCSVs). HCSVs are prepared by loading ascorbic acid (AA) in the core and poly(lactic-co-glycolic acid) shell incorporating iron oxide nanocubes (IONCs). MF triggers the release of AA, resulting in the increase of ferrous ions through the redox reaction between AA and IONCs. A significant tumor suppression is achieved by Fenton reaction-mediated ferroptosis-like cell-death. The oxidative stress induced by the Fenton reaction leads to the exposure of calreticulin on tumor cells, which leads to dendritic cells maturation and the infiltration of cytotoxic T lymphocytes in tumor. Furthermore, the depletion of ferric ions during treatment enables monitoring of the Fe reaction in MRI-R2* signal change. This strategy provides a perspective on ferroptosis-based immunotherapy.
我们提出了一种策略,通过外加的圆偏振磁场(MF)来增强芬顿反应,从而引发类铁死亡的细胞死亡,并通过使用混合核壳囊泡(HCSVs)赋予响应性 MRI 能力。HCSVs 通过在核内装载抗坏血酸(AA)和聚(乳酸-共-乙醇酸)壳内装载氧化铁纳米立方(IONCs)来制备。MF 触发 AA 的释放,通过 AA 和 IONCs 之间的氧化还原反应导致亚铁离子的增加。通过 Fenton 反应介导的类铁死亡细胞死亡实现了显著的肿瘤抑制。Fenton 反应引起的氧化应激导致钙网蛋白在肿瘤细胞上的暴露,从而导致树突状细胞成熟和细胞毒性 T 淋巴细胞在肿瘤中的浸润。此外,在治疗过程中铁离子的耗竭使得能够在 MRI-R2*信号变化中监测 Fe 反应。该策略为基于铁死亡的免疫治疗提供了新视角。
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