Red blood cell biomimetic nanoparticle with anti-inflammatory, anti-oxidative and hypolipidemia effect ameliorated atherosclerosis therapy

A main pathogenic factor of atherosclerosis is the local oxidative stress microenvironment. Probucol (PU) has anti-inflammatory, antioxidative and hypolipidemic effects, showing great potential to treat atherosclerosis. However, its low bioavailability limits its development. Herein, PU was encapsulated to form RP-PU with star-shaped polymers and red blood cell membranes. Star-shaped polymers show lower solution viscosity, a smaller hydrodynamic radius and a higher drug loading content than linear polymers. RP-PU had a good sustained-release effect and excellent biocompatibility. RP-PU can be efficiently internalized by cells to improve biodistribution. ApoE-/- mice were treated with RP-PU, and the contents of lipids and related metabolic enzymes were effectively reduced. The collagen fibers in the aortic root sections were reduced by RP-PU compared with control and PU. Moreover, RP-PU inhibited foam cell formation, decreased ICAM-1 and MCP-1 expression and delayed lesion formation. Consequently, RP-PU biomimetic nanoparticles can be developed as an anti atherosclerotic nanotherapeutic.(C) 2022 Elsevier Inc. All rights reserved.