Boosting Ferroptosis Therapy with Iridium Single-Atom Nanocatalyst in Ultralow Metal Content,Advanced Materials

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Boosting Ferroptosis Therapy with Iridium Single-Atom Nanocatalyst in Ultralow Metal Content
Advanced Materials ( IF 27.4 ) Pub Date : 2023-01-31 , DOI: 10.1002/adma.202210037
Junjie Cheng ₁ , Li Li ₂ , Duo Jin ₁ , Yi Dai ₃ , Yang Zhu _{4,

5,

6,

7} , Jianhua Zou _{4,

5,

6,

7} , Manman Liu ₁ , Wenxin Yu ₁ , Jiaji Yu ₁ , Yongfu Sun ₂ , Xiaoyuan Chen _{4,

5,

6,

7} , Yangzhong Liu ₁

Affiliation

Nanocatalysts are promising tumor therapeutics due to their ability to induce reactive oxygen species in the tumor microenvironment. Although increasing metal loading can improve catalytic activity, the quandary of high metal content versus potential systemic biotoxicity remains challenging. Here, a fully exposed active site strategy by site-specific anchoring of single iridium (Ir) atoms on the outer surface of a nitrogen-doped carbon composite (Ir single-atom catalyst (SAC)) is reported to achieve remarkable catalytic performance at ultralow metal content (≈0.11%). The Ir SAC exhibits prominent dual enzymatic activities to mimic peroxidase and glutathione peroxidase, which catalyzes the conversion of endogenous H₂O₂ into •OH in the acidic TME and depletes glutathione (GSH) simultaneously. With an advanced support of GSH-trapping platinum(IV) and encapsulation with a red-blood-cell membrane, this nanocatalytic agent (Pt@IrSAC/RBC) causes intense lipid peroxidation that boosts tumor cell ferroptosis. The Pt@IrSAC/RBC demonstrates superior therapeutic efficacy in a mouse triple-negative mammary carcinoma model, resulting in complete tumor ablation in a single treatment session with negligible side effects. These outcomes may provide valuable insights into the design of nanocatalysts with high performance and biosafety for biomedical applications.

中文翻译：

超低金属含量的铱单原子纳米催化剂促进铁死亡治疗

纳米催化剂因其在肿瘤微环境中诱导活性氧的能力而成为有前途的肿瘤治疗方法。尽管增加金属负载量可以提高催化活性，但高金属含量与潜在的全身生物毒性之间的困境仍然具有挑战性。据报道，通过将单个铱（Ir）原子定点锚定在氮掺杂碳复合材料（Ir单原子催化剂（SAC））的外表面上，采用完全暴露的活性位点策略，可以在超低催化温度下实现显着的催化性能。金属含量（约0.11%）。Ir SAC 表现出显着的双酶活性，可模拟过氧化物酶和谷胱甘肽过氧化物酶，在酸性 TME 中催化内源性 H ₂ O _{2转化为·OH，同时消耗谷胱甘肽 (GSH)。}这种纳米催化剂 (Pt@IrSAC/RBC) 具有 GSH 捕获铂 (IV) 的先进支持和红细胞膜封装，可引起强烈的脂质过氧化反应，从而促进肿瘤细胞铁死亡。Pt@IrSAC/RBC 在小鼠三阴性乳腺癌模型中表现出卓越的治疗效果，在单次治疗中即可完全消除肿瘤，且副作用可忽略不计。这些结果可能为生物医学应用中具有高性能和生物安全性的纳米催化剂的设计提供有价值的见解。

更新日期：2023-01-31

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