{"title":"Fe/Al‐LDH Nanomedicine for Antitumor Ferroptosis‐Immunotherapy by Immunosuppression Reversal","authors":"Wenming Fang, Zhiguo Yu, Ping Hu, Jianlin Shi","doi":"10.1002/adfm.202405483","DOIUrl":null,"url":null,"abstract":"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.","PeriodicalId":112,"journal":{"name":"Advanced Functional Materials","volume":null,"pages":null},"PeriodicalIF":18.5000,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advanced Functional Materials","FirstCategoryId":"88","ListUrlMain":"https://doi.org/10.1002/adfm.202405483","RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
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.
铁突变被认为是一种新型的程序性细胞死亡,具有高效的免疫原性,可激活 T 细胞介导的适应性免疫反应。然而,传统的铁凋亡诱导剂由于在免疫调节方面的效力较低,因此大多效果不佳。此外,肿瘤微环境中的 M2 型巨噬细胞对 T 细胞的抑制进一步削弱了铁氧体诱导的免疫治疗效果。为了克服这些挑战,本文报道了一种极其简单的铁/铝层双氢氧化物(Fe/Al-LDH)纳米药物,该药物能在酸性微环境中选择性降解,诱导肿瘤细胞铁突变,同时利用肿瘤细胞铁突变和巨噬细胞 M1 极化协同增强 T 细胞免疫反应,从而逆转免疫抑制微环境。这种组合策略在正位双侧乳腺癌模型中取得了良好的疗效,证明了铁/铝层双氢氧化物纳米平台在铁离子调控的癌症免疫疗法中的巨大应用潜力。
期刊介绍:
Firmly established as a top-tier materials science journal, Advanced Functional Materials reports breakthrough research in all aspects of materials science, including nanotechnology, chemistry, physics, and biology every week.
Advanced Functional Materials is known for its rapid and fair peer review, quality content, and high impact, making it the first choice of the international materials science community.