Ferroptosis is recognized as a novel type of programmed cell death with efficient immunogenicity to activate T cell‐mediated adaptive immune responses. However, conventional ferroptosis‐inducers mostly show poor efficacies due to their less effectiveness in immune regulation. In addition, suppression of T cells by M2‐type macrophages within the tumor microenvironment further weaken the immunotherapeutic effect of ferroptosis. To overcome these challenges, herein, an extremely simple Fe/Al‐layered double hydroxide (Fe/Al‐LDH) nanomedicine of enhanced iron concentration is reported, which is capable of selective degradation in acidic microenvironments to induce tumor cell ferroptosis and in the meantime reversing the immunosuppressive microenvironment by utilizing tumor cell ferroptosis and macrophage M1 polarization to synergistically enhance T cell immune response. This combined strategy has achieved excellent therapeutic efficacy in an orthotopic bilateral breast cancer model, demonstrating the great application potential of Fe/Al‐layered double hydroxide nanoplatform for iron ions‐regulated cancer immunotherapy.

中文翻译：

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Fe/Al-LDH 纳米药物通过逆转免疫抑制进行抗肿瘤铁死亡免疫治疗


铁死亡被认为是一种新型的程序性细胞死亡，具有有效的免疫原性，可以激活 T 细胞介导的适应性免疫反应。然而，传统的铁死亡诱导剂大多由于其免疫调节效果较差而表现出较差的效果。此外，肿瘤微环境中M2型巨噬细胞对T细胞的抑制进一步削弱了铁死亡的免疫治疗作用。为了克服这些挑战，本文报道了一种极其简单的铁浓度较高的铁/铝层状双氢氧化物（Fe/Al-LDH）纳米药物，它能够在酸性微环境中选择性降解，诱导肿瘤细胞铁死亡，同时利用肿瘤细胞铁死亡和巨噬细胞 M1 极化来逆转免疫抑制微环境，协同增强 T 细胞免疫反应。这种联合策略在原位双侧乳腺癌模型中取得了优异的治疗效果，证明了铁/铝层状双氢氧化物纳米平台在铁离子调节的癌症免疫治疗中的巨大应用潜力。