Nanotraps Based on Composite CeO2/Ulinastatin/Gallic Acid Nanoparticles for Capturing and Inactivating Lipopolysaccharides for the Treatment of Sepsis

Given that 30% to 80% of sepsis is related to lipopolysaccharide (LPS), scavenging LPS while exerting strong anti-inflammatory functions is of great significance. In the present study, a nanoparticle assembled from CeO2, ulinastatin (UTI), and gallic acid (GA). This nanoparticle can not only immediately bind with LPS to reduce LPS concentration but can also continuously exert the action of phosphatase to realize the dephosphorylation of LPS, which is named as nanotrap (NTp). NTp that can capture and inactivate LPS will block the binding of LPS to TLR4 receptors in cells, thereby limiting the subsequent inflammatory storm. In addition, NTp with the content of 500 μg/mL can eliminate over ∼50% of H2O2 within 60 min while generating O2, indicating its CAT mimetic-enzyme activity. At the same time, UTI in NTp plays a role in reducing inflammation. NTp promotes M2 polarization of macrophages and inhibits TLR4/NF-κB expression and inflammation in vivo, exhibiting a well-performed therapeutic effect on mice with LPS-induced sepsis, including a significantly lower mortality rate and organ damage repair.