Synthetic CD47 antibody-chitosan/hyaluronic acid polyelectrolyte complex mediates targeted inhibition of atherosclerotic plaques by exogenous foam-like cells via the NLRP3 pathway

Abstract

Studies have shown that CD47-mediated macrophage immune escape plays an important role in the formation of atherosclerotic plaques. CD47 is the target of an atherosclerosis treatment strategy that promotes the body’s clearance of macrophages in atherosclerotic plaques, via a mechanism that improves the immune system’s recognition of foam-like cells, which are derived from macrophages that highly express CD47. We designed a synthetic CD47 antibody coated with hyaluronic acid and chitosan nanocarriers to coat foreign foam cells, which we administered to high-fat-fed apoE knockout mice to study their atherosclerotic plaques using block inhibition. In vitro, we synthesized CD47 hyaluronic acid-modified chitosan nanoparticles and tested their physical and chemical properties, stability, cytotoxicity, and targeting patterns. Then, CD47 nanoparticles were coated with exogenous foam cells and given to high-fat-fed mice. The apoE knockout mice were then observed and analyzed. CD47 nanoparticles had good biostability, no obvious cytotoxicity, and adequate in vivo and in vitro targeting. Further experiments showed that the foreign foam cells were coated. Our observations revealed that CD47 nanoparticle-coated exogenous cells may partially mediate the inhibition of atherosclerotic plaques by activating NLRP3-related signaling pathways. Our experiments showed that CD47 hyaluronic acid-modified chitosan nanoparticles can mediate the inhibition of atherosclerotic plaques generated by exogenous foam cells through the NLRP3 pathway, providing a basis for the potential application of a treatment for atherosclerotic plaques.