Tumor Microenvironment-Activated Nanoparticles Loaded with an Iron-Carbonyl Complex for Chemodynamic Immunotherapy of Lung Metastasis of Melanoma In Vivo,ACS Applied Materials & Interfaces

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Tumor Microenvironment-Activated Nanoparticles Loaded with an Iron-Carbonyl Complex for Chemodynamic Immunotherapy of Lung Metastasis of Melanoma In Vivo
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2021-08-12 , DOI: 10.1021/acsami.1c11485
Tianli Zhai ₁ , Wei Zhong ₂ , Yucong Gao ₁ , Han Zhou ₁ , Zhiguo Zhou ₁ , Xiaoming Liu ₂ , Shiping Yang ₁ , Hong Yang ₁

Affiliation

In this work, a nanoplatform (FeCORM NPs) loaded with an iron-carbonyl complex was constructed. By exploiting chemodynamic therapy (CDT) and immunogenic cell death (ICD)-induced immunotherapy (IMT), the nanoparticles exhibited excellent efficacy against lung metastasis of melanoma in vivo. The iron-carbonyl compound of the nanomaterials could be initiated by both glutathione (GSH) and hydrogen peroxide (H₂O₂) to release CO and generate ferrous iron through ligand exchange and oxidative destruction pathways. The released CO caused mitochondria damage, whereas the generated ferrous iron led to oxidative stress via the Fenton reaction. On the other hand, the nanomaterials induced ICD-based IMT, which worked jointly with CDT to exhibit excellent effects against lung metastasis of melanoma through a mouse model. This work demonstrated how a nanoplatform, simple and stable but showing excellent efficacy against tumors, could be built using simple building blocks via a self-assembling approach. Importantly, the system took advantage of relatively high levels of GSH and H₂O₂ in tumors to initiate the therapeutic effects, which rendered the nanoplatform with a capability to differentiate normal cells from tumor cells. In principle, the system has great potential for future clinical applications, not only in the treatment of lung metastasis of melanoma but also in suppressing other types of tumors.

中文翻译：

载有铁-羰基复合物的肿瘤微环境激活纳米颗粒用于体内黑色素瘤肺转移的化学动力学免疫治疗

在这项工作中，构建了一个装载有铁羰基复合物的纳米平台（FeCORM NPs）。通过利用化学动力学疗法 (CDT) 和免疫原性细胞死亡 (ICD) 诱导的免疫疗法 (IMT)，纳米颗粒在体内对黑色素瘤的肺转移表现出优异的疗效。纳米材料的铁羰基化合物可由谷胱甘肽（GSH）和过氧化氢（H ₂ O ₂）引发，通过配体交换和氧化破坏途径释放CO并生成亚铁。释放的 CO 导致线粒体损伤，而产生的亚铁则通过芬顿反应。另一方面，纳米材料诱导基于 ICD 的 IMT，它与 CDT 共同作用，通过小鼠模型对黑色素瘤的肺转移表现出优异的效果。这项工作展示了如何通过自组装方法使用简单的构建块构建简单稳定但对肿瘤具有出色功效的纳米平台。重要的是，该系统利用了相对较高水平的 GSH 和 H ₂ O ₂在肿瘤中启动治疗效果，这使得纳米平台具有区分正常细胞和肿瘤细胞的能力。原则上，该系统在未来的临床应用中具有巨大的潜力，不仅在治疗黑色素瘤的肺转移方面，而且在抑制其他类型的肿瘤方面。

更新日期：2021-08-25

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