Functional resveratrol-biodegradable manganese doped silica nanoparticles for the spinal cord injury treatment

Mater Today Bio. 2021 Dec 4:13:100177. doi: 10.1016/j.mtbio.2021.100177. eCollection 2022 Jan.

Abstract

Spinal cord injury (SCI) causes secondary injury, accompanied by pathological changes such as oxidative stress, inflammation and neuronal apoptosis. This leads to permanent disabilities such as paralysis and loss of movement or sensation. Due to the ineffectiveness of drugs passing through the blood spinal cord barrier (BSCB), there is currently no effective treatment for SCI. The aim of this experiment was to design plasma complex component functionalized manganese-doped silica nanoparticles (PMMSN) with a redox response as a targeted drug carrier for resveratrol (RES), which effectively transports insoluble drugs to cross the BSCB. RES was adsorbed into PMMSN with a particle size of approximately 110 ​nm by the adsorption method, and the drug loading reached 32.61 ​± ​3.38%. The RES release results for the loaded sample (PMMSN-RES) showed that the PMMSN-RES exhibited a release slowly effect. In vitro and vivo experiments demonstrated that PMMSN-RES decreased reactive oxygen species (ROS) and malondialdehyde (MDA), increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, reduced the expression of inflammatory (TNF-α, IL-1β and IL-6) and apoptotic cytokines (cleaved caspase-3) in spinal cord tissue after SCI. In summary, PMMSN-RES may be a potential pharmaceutical preparation for the treatment of SCI by reducing neuronal apoptosis and inhibiting inflammation caused by reducing oxidative stress to promote the recovery of mouse motor function.

Keywords: BSCB, blood spinal cord barrier; GSH-Px, glutathione peroxidase; H2O2, hydrogen peroxide; MDA, malondialdehyde; MMSN, manganese-doped mesoporous silica nanoparticles; Manganese-doped silica nanoparticles; MnO2, manganese dioxide; Neuronal apoptosis; Oxidative stress; PMMSN, plasma complex component functionalized manganese-doped silica nanoparticles; RES, resveratrol; ROS, reactive oxygen species; Redox response; Resveratrol; SCI, spinal cord injury; SOD, increased superoxide dismutase; Spinal cord injury.