Renal Clearable Ultrasmall Single-Crystal Fe Nanoparticles for Highly Selective and Effective Ferroptosis Therapy and Immunotherapy,Journal of the American Chemical Society

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Renal Clearable Ultrasmall Single-Crystal Fe Nanoparticles for Highly Selective and Effective Ferroptosis Therapy and Immunotherapy
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2021-09-02 , DOI: 10.1021/jacs.1c07471
Huan Liang ₁ , Xiyao Wu ₁ , Guizhen Zhao ₁ , Kai Feng ₁ , Kaiyuan Ni ₂ , Xiaolian Sun ₁

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Iron-based nanoparticles have attracted much attention because of their ability to induce ferroptosis via a catalyzing Fenton reaction and to further potentiate immunotherapy. However, current iron-based nanoparticles need to be used in cooperation with other treatments or be applied in a high dose for effective therapy because of their low reactive oxygen species production efficacy. Here, we synthesized ultrasmall single-crystal Fe nanoparticles (bcc-USINPs) that stayed stable in a normal physiological environment but were highly active in a tumor microenvironment because of the selective acidic etching of an Fe₃O₄ shell and the exposure of the Fe(0) core. The bcc-USINPs could efficiently induce tumor cell ferroptosis and immunogenetic cell death at a very low concentration. Intravenous injection of iRGD-bcc-USINPs at three doses of 1 mg/kg could effectively suppress the tumor growth, promote the maturation of dendritic cells, and trigger the adaptive T cell response. Combined with programmed death-ligand 1 (PD-L1) immune checkpoint blockade immunotherapy, the iRGD-bcc-USINP-mediated ferroptosis therapy greatly potentiated the immune response and developed strong immune memory. In addition, these USINPs were quickly renal excreted with no side effects in normal tissues. These iRGD-bcc-USINPs provide a simple, safe, effective, and selectively tumor-responsive Fe(0) delivery system for ferroptosis-based immunotherapy.

中文翻译：

用于高选择性和有效铁死亡治疗和免疫治疗的肾脏可清除超小单晶 Fe 纳米颗粒

铁基纳米粒子因其通过催化芬顿反应诱导铁死亡和进一步增强免疫治疗的能力而备受关注。然而，目前的铁基纳米粒子由于其活性氧产生效率低，需要与其他治疗配合使用或以高剂量应用以进行有效治疗。在这里，我们合成了超小单晶 Fe 纳米粒子 (bcc-USINPs)，该纳米粒子在正常生理环境中保持稳定，但由于 Fe ₃ O _{4的选择性酸性蚀刻，在肿瘤微环境中具有高度活性。}壳和 Fe(0) 核的暴露。bcc-USINPs 可以在非常低的浓度下有效地诱导肿瘤细胞铁死亡和免疫细胞死亡。iRGD-bcc-USINPs 1 mg/kg 3次静脉注射可有效抑制肿瘤生长，促进树突状细胞成熟，触发适应性T细胞反应。结合程序性死亡配体 1 (PD-L1) 免疫检查点阻断免疫疗法，iRGD-bcc-USINP 介导的铁死亡疗法极大地增强了免疫反应并产生了强大的免疫记忆。此外，这些 USINP 可迅速从肾脏排出，对正常组织没有副作用。这些 iRGD-bcc-USINP 为基于铁死亡的免疫治疗提供了一种简单、安全、有效和选择性的肿瘤响应性 Fe(0) 递送系统。

更新日期：2021-09-29

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