Fe-Curcumin Nanozyme-Mediated Reactive Oxygen Species Scavenging and Anti-Inflammation for Acute Lung Injury,ACS Central Science

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Fe-Curcumin Nanozyme-Mediated Reactive Oxygen Species Scavenging and Anti-Inflammation for Acute Lung Injury
ACS Central Science ( IF 12.7 ) Pub Date : 2021-12-02 , DOI: 10.1021/acscentsci.1c00866
Renyikun Yuan _{1,

2} , Yuqing Li ₃ , Shan Han ₁ , Xinxin Chen ₁ , Jingqi Chen ₄ , Jia He ₁ , Hongwei Gao ₁ , Yang Yang _{3,

5} , Shilin Yang ₁ , Yu Yang ₄

Affiliation

Pneumonia, such as acute lung injury (ALI), has been a type of lethal disease that is generally caused by uncontrolled inflammatory response and excessive generation of reactive oxygen species (ROS). Herein, we report Fe-curcumin-based nanoparticles (Fe-Cur NPs) with nanozyme functionalities in guiding the intracellular ROS scavenging and meanwhile exhibiting anti-inflammation efficacy for curing ALI. The nanoparticles are noncytotoxic when directing these biological activities. Mechanism studies for the anti-inflammation aspects of Fe-Cur NPs were systematically carried out, in which the infected cells and tissues were alleviated through downregulating levels of several important inflammatory cytokines (such as TNF-α, IL-1β, and IL-6), decreasing the intracellular Ca²⁺ release, inhibiting NLRP3 inflammasomes, and suppressing NF-κB signaling pathways. In addition, we performed both the intratracheal and intravenous injection of Fe-Cur NPs in mice experiencing ALI and, importantly, found that the accumulation of such nanozymes was enhanced in lung tissue (better than free curcumin drugs), demonstrating its promising therapeutic efficiency in two different administration methods. We showed that the inflammation reduction of Fe-Cur NPs was effective in animal experiments and that ROS scavenging was also effectively achieved in lung tissue. Finally, we revealed that Fe-Cur NPs can decrease the level of macrophage cells (CD11b^loF4/80^hi) and CD3⁺CD45⁺ T cells in mice, which could help suppress the inflammation cytokine storm caused by ALI. Overall, this work has developed the strategy of using Fe-Cur NPs as nanozymes to scavenge intracellular ROS and as an anti-inflammation nanodrugs to synergistically cure ALI, which may serve as a promising therapeutic agent in the clinical treatment of this deadly disease. Fe-Cur NP nanozymes were designed to attenuate ALI by clearing intracellular ROS and alleviating inflammation synergistically. Relevant cytokines, inflammasomes, and signaling pathways were studied.

中文翻译：

铁姜黄素纳米酶介导的活性氧清除和抗炎治疗急性肺损伤

肺炎，例如急性肺损伤（ALI），是一种致命疾病，通常是由不受控制的炎症反应和活性氧（ROS）过度产生引起的。在此，我们报道了具有纳米酶功能的基于铁姜黄素的纳米粒子（Fe-Cur NPs）可以引导细胞内ROS清除，同时表现出抗炎功效，用于治疗ALI。纳米粒子在指导这些生物活动时是无细胞毒性的。系统地开展了 Fe-Cur NPs 抗炎作用的机制研究，通过下调几种重要炎症细胞因子（如 TNF-α、IL-1β 和 IL-6）的水平来缓解受感染的细胞和组织。 )，减少细胞内Ca ²⁺释放，抑制NLRP3炎症小体，抑制NF-κB信号通路。此外，我们对患有 ALI 的小鼠进行了气管内和静脉注射 Fe-Cur NP，重要的是，发现这种纳米酶在肺组织中的积累得到增强（优于游离姜黄素药物），这证明了其在两种不同的给药方法。我们表明，Fe-Cur NPs 在动物实验中可以有效减少炎症，并且在肺组织中也可以有效地清除 ROS。最后，我们发现 Fe-Cur NPs 可以降低小鼠巨噬细胞 (CD11b ^lo F4/80 ^hi ) 和 CD3 ⁺ CD45 ⁺ T 细胞的水平，这有助于抑制 ALI 引起的炎症细胞因子风暴。总体而言，这项工作开发了使用 Fe-Cur NPs 作为纳米酶清除细胞内 ROS 和作为抗炎纳米药物来协同治疗 ALI 的策略，这可能成为临床治疗这种致命疾病的一种有前途的治疗剂。 Fe-Cur NP 纳米酶旨在通过协同清除细胞内 ROS 和减轻炎症来减轻 ALI。研究了相关的细胞因子、炎症小体和信号通路。

更新日期：2022-01-26

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