Background and Aims: Theranostics is an emerging concept of integrating therapy and imaging into a single platform. Intracerebral hemorrhage (ICH) causes intense inflammation by toxic effect of hematoma itself and mechanical disruption of brain tissue, which is a promising target of theranostics. We developed a novel theranostic protocells loaded with cerium oxide nanoparticles (CeNPs) for treatment and iron-oxide nanoparticles (FeNPs) for imaging.
Method: We synthesized 100-nm mesoporous silica nanoparticle (MSN) as a bio-compatiable nanocarrier, incorporated FeNPs in the core and CeNPs on the surface, and encapsulated MSN with lipid bilayer. Reactive oxygen species (ROS) scavenging and cytoprotective effects of the protocells were assessed in RAW264.7 cells. Brain water content, macrophage infiltration, and behavior function (corner turn and forelimb use asymmetry) were measured in collagenase-induced rodent ICH model after injecting the protocells. Serial brain MR imaging was also performed to confirm diagnostic ability of working site of protocells.
Results: The protocells were monodisperse in water and highly loaded with CeNPs, which exhibited a strong ROS scavenging (-26%, P<0.05) and cytoprotective effects (-51%, P<0.01). The protocells reduced macrophage infiltration (-58%, P<0.01) and brain edema (-1% water content, P<0.01) and improved neurologic outcome (+15% corner turn, P<0.05). In serial T2-weighted MR imaging, the protocells that reached peri-hematomal area were clearly visualized.
Conclusions: As the first theranostic nanobiomaterial, our protocells successfully visualized its working site in peri-hematomal area by MR imaging, and improved inflammatory status and neurologic outcomes after ICH. Beyond its potential for ICH theranosis, protocells could be generalized to other inflammatory diseases.