Engineered Multifunctional Zinc–Organic Framework-Based Aggregation-Induced Emission Nanozyme for Accelerating Spinal Cord Injury Recovery

Abstract

Functional recovery following a spinal cord injury (SCI) is challenging. Traditional drug therapies focus on the suppression of immune responses; however, strategies for alleviating oxidative stress are lacking. Herein, we developed the zinc−organic framework (Zn@MOF)-based aggregationinduced emission−active nanozymes for accelerating recovery following SCI. A multifunctional Zn@MOF was modified with the aggregation-induced emission−active molecule 2-(4-azidobutyl)-6-(phenyl(4-(1,2,2-triphenylvinyl)phenyl)amino)-1Hphenalene-1,3-dione via a bioorthogonal reaction, and the resulting nanozymes were denoted as Zn@MOF-TPD. These nanozymes gradually released gallic acid and zinc ions (Zn 2+ ) at the SCI site. The released gallic acid, a scavenger of reactive oxygen species (ROS), promoted antioxidation and alleviated inflammation, re-establishing the balance between ROS production and the antioxidant defense system. The released Zn 2+ ions inhibited the activity of matrix metalloproteinase 9 (MMP-9) to facilitate the regeneration of neurons via the ROS-mediated NF-κB pathway following secondary SCI. In addition, Zn@MOF-TPD protected neurons and myelin sheaths against trauma, inhibited glial scar formation, and promoted the proliferation and differentiation of neural stem cells, thereby facilitating the repair of neurons and injured spinal cord tissue and promoting functional recovery in rats with contusive SCI. Altogether, this study suggests that Zn@MOF-TPD nanozymes possess a potential for alleviating oxidative stress-mediated pathophysiological damage and promoting motor recovery following SCI.

Nanozymes: Potential Therapies for Reactive Oxygen Species Overproduction and Inflammation in Ischemic Stroke and Traumatic Brain Injury

“…At present, the application of nanozymes in TBI and ischemic stroke is still immature and needs to be further explored and verified. Similar to acute brain injury, Alzheimer’s disease, Spinal cord injury, and Parkinson’s disease are oxidation-damaging diseases. − The current article shows that some nanozymes have been used to treat Alzheimer’s disease, Spinal cord injury, and Parkinson’s disease. ,− In the future, we can expect that the nanozymes used in these oxidative damage diseases can be improved to make the application more extensive.…”

Employing Spectroscopic, Electrochemical, and In Silico Research to Investigate the Interaction of Ofloxacin, Antibacterial Drug With the Haemoglobin

“…Then, the structure of Hb with PDB ID: 2DN1 was taken from RCSB database (https://www.rcsb.org/) and prepared appropriately using another computational tool, Chimera 1.8. [21,22] Preparation of protein is necessary to get satisfactory results. BIOVIA Discovery Studio Visualizer was used to visualize the conformation and interactions of ofloxacin with Hb.…”

Enhancing anti-neuroinflammation effect of X-ray-triggered RuFe-based metal-organic framework with dual enzyme-like activities

“…Drugs with strong antioxidant effects and superior biocompatibility are required for effective treatment of SCI. Nanozymes possessing enzyme-mimetic activities have attracted substantial attention in the treatment of oxidative stress-related diseases, such as diabetic wounds, osteoarthritis, and SCI (Zheng et al, 2024). Advances in nanozyme development may introduce some methods for applying biomedicine to the treatment of intractable inflammatory diseases, including traumatic spinal cord injury (Jiang et al, 2023).…”

“…Oxidative stress and inflammation are central pathophysiological processes in a traumatic spinal cord injury. Antioxidant therapies that reduce the reactive oxygen and nitrogen species (RONS) overgeneration and inflammation are proved promising for improving the outcomes (Wang Z. et al, 2022;Wu et al, 2023a;Chen et al, 2024). However, efficient and long-lasting antioxidant therapy to eliminate multiple RONS with effective neuroprotection remains challenging (Wu et al, 2023b;Wu et al, 2023c;Hou et al, 2024).…”