Customized lipid-coated magnetic mesoporous silica nanoparticle doped with ceria nanoparticles for theragnosis of intracerebral hemorrhage

Intracerebral hemorrhage （ICH）, caused by the sudden rupture of an artery within the brain, is a devastating subtype of stroke, which currently has no effective treatment. Intense inflammatory reactions that occur in the peri-hematomal area after ICH are more deleterious than the hematoma itself, resulting in subsequent brain edema and neurologic deterioration. Thus, we developed lipid-coated magnetic mesoporous silica nanoparticles doped with ceria nanoparticles （CeNPs）, abbreviated as LMCs, which have both potent anti-inflammatory therapeutic effects via scavenging reactive oxygen species and help in increasing the efficacy of magnetic resonance imaging enhancement in the peri-hematomal area. LMCs consist of mesoporous silica nanopartide-supported lipid bilayers, which are loaded with large amounts of CeNPs for scavenging of reactive oxygen species, and iron oxide nanoparticles for magnetic resonance imaging contrast. LMCs loaded with CeNPs exhibited strong anti-oxidative and anti-inflammatory activities in vitro. In the rodent ICH model, intracerebraUy injected LMCs reached the peri-hematomal area and were engulfed by macrophages, which were clearly visualized by magnetic resonance imaging of the brain. Moreover, LMCs reduced inflammatory macrophage infiltration, and thus significantly reduced brain edema. Finally, LMC treatment markedly improved neurologic outcomes of the animals with ICH. Thus, LMC is the first nanobiomaterial that successfully showed theragnostic effects in ICH.

Biocompatible custom ceria nanoparticles against reactive oxygen species resolve acute inflammatory reaction after intracerebral hemorrhage

Intracerebral hemorrhage （ICH） is a devastating subtype of stroke with a high mortality rate, for which there currently is no effective treatment. A perihematomal edema caused by an intense inflammatory reaction is more deleterious than the hematoma itself and can result in neurological deterioration and death. Ceria nanoparticles （CeNPs） are potent free radical scavengers with potential for biomedical applications. As oxidative stress plays a major role in post-ICH inflammation, we hypothesized that CeNPs might protect against ICH. To test this hypothesis, core CeNPs were synthesized using a modified reverse micelle method and covered with phospholipid-polyethylene glycol （PEG） to achieve biocompatibility. We investigated whether our custom-made biocompatible CeNPs have protective effects against ICH. The CeNPs reduced oxidative stress, hemin-induced cytotoxicity, and inflammation in vitro. In a rodent ICH model, intravenously administered CeNPs were mainly distributed in the hemorrhagic hemisphere, suggesting that they could diffuse through the damaged blood-brain barrier. Moreover, CeNPs attenuated microglia/macrophage recruitment around the hemorrhagic lesion and inflammatory protein expression. Finally, CeNP treatment reduced the brain edema by 68.4% as compared to the control. These results reveal the great potential of CeNPs as a novel therapeutic agent for patients with ICH.