The treatment value of IL-1β monoclonal antibody under the targeting location of alpha-methyl- l -tryptophan and superparamagnetic iron oxide nanoparticles in an acute temporal lobe epilepsy model

摘要

Temporal lobe epilepsy (TLE) is a common and often refractory brain disease that is closely correlated with inflammation. Alpha-methyl-l-tryptophan (AMT) is recognized as a surrogate marker for epilepsy, characterized by high uptake in the epileptic focus. There are many advantages of using the magnetic targeting drug delivery system of superparamagnetic iron oxide nanoparticles (SPIONs) to treat many diseases, including epilepsy. We hypothesized that AMT and an IL-1β monoclonal antibody (anti-IL-1β mAb) chelated to SPIONs would utilize the unique advantages of SPIONs and AMT to deliver the anti-IL-1β mAb across the blood–brain barrier (BBB) as a targeted therapy. Acute TLE was induced in 30 rats via treatment with lithium-chloride pilocarpine. The effects of plain-SPIONs, anti-IL-1β-mAb-SPIONs, or AMT-anti-IL-1β-mAb-SPIONs on seizure onset were assessed 48?h later. Perl’s iron staining, Nissl staining, immunofluorescence staining and western blotting were performed after magnetic resonance imaging examination. The imaging and histopathology in combination with the molecular biology findings showed that AMT-anti-IL-1β-mAb-SPIONs were more likely to penetrate the BBB in the acute TLE model to reach the targeting location and deliver a therapeutic effect than plain-SPIONs and anti-IL-1β-mAb-SPIONs. This study demonstrated the significance of anti-IL-1β-mAb treatment in acute TLE with respect to the unique advantages of SPIONs and the active location-targeting characteristic of AMT.