Inflammatory Microenvironment‐Responsive Nanomaterials Promote Spinal Cord Injury Repair by Targeting IRF5. Issue 23 (10th October 2022)

• Record Type: Journal Article
• Authors: Ma, Dezun; Shen, He; Chen, Fangman; Liu, Weiyuan; Zhao, Yannan; Xiao, Zhifeng; Wu, Xianming; Chen, Bing; Lu, Junna; Shao, Dan; Dai, Jianwu
• Is Part Of: Advanced healthcare materials. Volume 11:Issue 23(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-10-10
• Subjects: immunomodulation -- IRF5 -- macrophages -- reactive oxygen species -- spinal cord injury; Biomedical materials -- Periodicals; 610.28
• DOI: 10.1002/adhm.202201319
• Languages: English
• ISSNs: 2192-2640

Abstract

Abstract: Spinal cord injury (SCI) involves excessive inflammatory responses, which are characterized by the existence of high levels of proinflammatory M1 macrophages rather than prohealing M2 macrophages, and oxidative stress. Interferon regulatory factor 5 (IRF5) is a promising therapeutic target in regulation of macrophage reprogramming from the M1 to M2 phenotype. However, knockdown of IRF5 expression mediated by small interfering RNA (siRNA) is limited by instability and poor cellular uptake. In the present study, polyethylenimine‐conjugated, diselenide‐bridged mesoporous silica nanoparticles are tailored to regulate macrophage polarization by controllably delivering siRNA to silence IRF5. The MSN provides reactive oxygen species (ROS)‐responsive degradation and release, while polyethylenimine‐function offers efficient loading of siRNA‐IRF5 and enhanced endosome escape. As a consequence, the intelligent nanomaterial effectively transfects the siRNA‐IRF5 with its remaining high stability and bioactivity, thereby effectively regulating the M1‐to‐M2 macrophage conversion in vitro and in vivo. Importantly, administration of the functional nanomaterial in crush SCI mice suppresses excessive inflammation, enhances neuroprotection, and promotes locomotor restoration. Collectively, the ROS‐responsive nanomedicine provides a gene silencing strategy for regulating macrophage polarization and oxidative balance in SCI repair. Abstract : A novel immunoregulatory nanomaterial with the capacities of reactive oxygen species (ROS) scavenging and responsive small interfering RNA (siRNA)–interferon regulatory factor 5 (IRF5) delivery for reprogramming M1‐to‐M2 macrophage polarization is developed with diselenide bonds and polyethyleneimine. Moreover, administration of this nanomaterial reduces the inflammatory response, enhances the neuronal protection and axon regeneration, and promotes functional recovery in crush spinal cord injury (SCI) mice.