Tocilizumab-loaded nanoparticles block IL-6R and reduce edema after intracerebral hemorrhage
Journal of Advanced Research, 2026
Ma S., Lin Q., Xue D., Li L., Liu H., Guo H., Sun F., Dong J., Guo C., Han L., Zhao J., Ma J., Wang Q., Guo W., Ge S., Tian Y., Zhou J., Qu Y.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Neurovascular Diseases | Technical Evaluation | Mouse Tissue Lysate |  Olink Target 96 Mouse |
Abstract
Introduction
Elevated plasma interleukin-6 (IL-6) is an independent prognostic predictor in patients with intracerebral hemorrhage (ICH). However, the therapeutic antibody tocilizumab (TCZ) is limited by its poor blood–brain barrier (BBB) penetrance.
Objectives
This research sought to explore the effects and mechanisms of TCZ-loaded nanoparticles on inflammatory injury and BBB disruption in ICH.
Methods
We conducted a retrospective study of ICH patients from our institution to determine whether an association exists between plasma IL-6 levels and the severity and prognosis of ICH in the Chinese population. We investigated the role of TCZ in ICH using a collagenase-induced mouse model and different administration methods. We developed brain-targeted nanoparticles (PLGA-TCZ@PEG-RVG29, marked as PTPR NPs) to deliver TCZ across the BBB.
Results
In a mouse model, intravenously administered PTPR NPs crossed the BBB, accumulated in perihematomal regions, and reduced perihematomal edema (PHE) while improving neurological function after ICH. Mechanistically, PTPR NPs attenuated neuroinflammation by suppressing ERK and NF-κB signaling, reducing neurotoxic A1 astrocytes while enhancing protective A2 phenotypes, and limiting peripheral immune cell infiltration and neutrophil extracellular trap formation. These effects preserved BBB integrity, reduced neuronal apoptosis, and protected white matter structure, promoting functional recovery after ICH.
Conclusion
Our findings demonstrate that PTPR NPs are an effective platform for targeted IL-6 receptor (IL-6R) blockade in ICH and suggest a potential for delivering biologics in other neuroinflammatory diseases.