Ceria/POMs hybrid nanoparticles as a mimicking metallopeptidase for treatment of neurotoxicity of amyloid b peptide.
Protein misfolding to amyloid aggregates is the hallmark for neurodegenerative disease. While much attention has been paid to screen natural proteases that can degrade amyloid b peptides (Ab) it is difficult to apply them in the clinics with the intractable problem of immunogenicity in living organisms. Herein, we rationally designed an artificial nanozyme, Ceria/Polyoxometalates hybrid (CeONP@POMs) with both proteolytic and superoxide dismutase (SOD) activities. Our results indicated that CeONP@POMs could efficiently degrade Ab aggregates and reduce intracellular reactive oxygen species (ROS) More importantly, CeONP@POMD could not only promote PC12 cell proliferation and can cross blood brain barrier (BBB) but also inhibit Ab induced BV2 microglial cell activation which was demonstrated by immunoluorescence assay and flow cytometry measurements. In vivo studies further indicated that CeONP@POMD as nanozyme possessed good biocompatibility, evidenced by a detailed study of their biodistribution, body weight change, and in vivo toxicology. Therefore, our results pave the way for design of multifunctional artificial nanozyme for treatment of neurotoxicity of amyloid b peptide.
Biomaterials