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

Renyikun Yuan; Yuqing Li; Shan Han; Xinxin Chen; Jingqi Chen; Jia He; Hongwei Gao; Yang Yang; Shilin Yang; Yu Yang

doi:10.1021/acscentsci.1c00866

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

ACS Cent Sci. 2022 Jan 26;8(1):10-21. doi: 10.1021/acscentsci.1c00866. Epub 2021 Dec 2.

Authors

Renyikun Yuan^{1

2}, Yuqing Li³, Shan Han¹, Xinxin Chen¹, Jingqi Chen⁴, Jia He¹, Hongwei Gao¹, Yang Yang^{3

5}, Shilin Yang¹, Yu Yang⁴

Affiliations

¹ College of Pharmacy, Guangxi University of Chinese Medicine, Nanning 530000, China.
² College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China.
³ Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, China.
⁴ Institute of Molecular Medicine (IMM), Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, China.
⁵ School of Materials Science and Engineering, Tongji University, Shanghai 201804, China.

Abstract

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.