A Novel Endoplasmic Reticulum-targeted Metal-Organic Framework-Confined Ruthenium (Ru) Nanozyme Regulation of Oxidative Stress for Central Post-Stroke Pain.

Central post-stroke pain (CPSP) is a chronic neuropathic pain caused by cerebrovascular lesion or disfunction after stroke. The available treatments for CPSP have either troublesome side effects or limited efficacy, therefore, further advancedment in therapeutic options is needed. Convincing evidence suggest that excessive reactive oxygen species (ROS), reactive nitrogen species (RNS), and generated matrix metalloproteinase (MMPs) are largely involved in the development of pain. In our current study, we report an effective strategy for treating pain hypersensitivity using an endoplasmic reticulum (ER)-targeted metal-organic framework (MOF)-confined ruthenium (Ru) nanozyme. The Ru MOF is coated with a p-dodecylbenzene sulfonamide (p-DBSN) modified liposome with endoplasmic reticulum-targeted function. Our analysis revealved that ROS, Emmprin, MMP-2, and MMP-9 were upregulated in the brain of CPSP mice, along with the elevated expression of inflammation markers such as TNF-α and IL-6. Compared to vehicle, one-time intravenous administrations of Ru MOF significantly reduced mechanical hypersensitivity after CPSP for three days. Overall, ER-Ru MOF system can inhibits oxidative stress in the brain tissues of CPSP model, reduce MMPs expression, and suppress inflammation response-induced injury, resulting in satisfactory prevention and effective treatment of CPSP during a hemorrhagic stroke. The ER-Ru MOF is expected to be useful for the treatment of not only CPSP but also other neurological diseases associated with the vicious activation of ROS, based on the generality of the approach used in this study. This article is protected by copyright. All rights reserved.