Inhibition Of Lanthanide Nanocrystal-induced Inflammasome Activation By A Surface Coating Peptide

Rare earth elements refer to the gegeric terms of fifteen kinds of lanthanide elements and the other two elements scandium (Sc) and yttrium (Y) in the chemical periodic table. Due to their excellently optical, electrical, magnetic and other features, rare earth materials are widely used in ceramics, luminescent materials, permanent magnet materials, environmental protection materials, catalyst materials, information science and biomedical sciences. As a kind of new biomaterial for biological labeling, rare earth upconversion luminescent nanomaterials with favorable biocompatibility are widely applied in biomedical engineering including biological drug delivery, biological imaging, biological detection and development of real-time diagnosis device. However, similar to other nanomaterials, rare earth nanoparticles are also facing urgent biological safety problems when they bring much convenience to people’s daily life. A variety of nanomaterials including rare earth nanoparticles activated NLRP3 inflammasome in macrophages, promoting the production and secretion of active caspase-1 and mature IL-1β and causing caspase-1-dependent pyroptosis. NLRP3 inflammasome was involved in diverse inflammatory disease, including type Ⅱ diabetes, atherosclerosis, gout and Alzheimer’s disease. RE-1 is a kind of rare earth particles-special surface coating peptide discovered with phage display in 2012. Here we show that RE-1 coating effectively inhibited rare earth particles-induced NLRP3 inflammasome activation in macrophages and also reduced rare earth nanoparticles-elicited inflammatory response in vivo. RE-1 coating had no influence on cell uptake of rare earth nanoparticles in BMDM cells, in contrast to the situation in HeLa cells where cellular internalization of rare earth nanoparticles was significantly inhibited by RE-1. RE-1 coating did not reduce potassium efflux, which occurred after rare earth particles treatment in BMDM cells and RE-1 did decrease lysosomal damage induced by LNs while the inhibitor of cathepsin B did not affect rare earth particles-elicited NLRP3 inflammsomes activation. Rare earth particles induced generation of a large number of ROS, then activated TRPM2 and triggered Ca2+ influx. Inhibition of ROS production, and the subsequent abrogation of TRPM2-mediated Ca2+ influx, is the primary mechanism underlying RE-1’s inhibitory effect on LNs-induced inflammasome activation. What’s more, RE-1 coating abrogated ROS generated from NADPH oxidase more than mitochondria-generated ROS in macrophages with the treatment of rare earth nanoparticles. Here, we provides a metahod to tightly controlling inflammation cuased by rare earth nanoparticles and improving the particles’biological safety through modification of a special coating peptide,which hold great value for in vivo application of rare earth nanoparticles and other engineering nanomaterials.