Biomimetic Ginsenoside Rb1 and Probucol Co-Assembled Nanoparticles for Targeted Atherosclerosis Therapy via Inhibition of Oxidative Stress, Inflammation, and Lipid Deposition.

To overcome the limitations of conventional oral drugs and nanocarrier-dependent delivery systems in atherosclerosis (AS) therapy, our work proposes an "integration of Chinese and Western medicine" approach to develop a new biomimetic traditional Chinese and Western medicine components coassembled nanoparticles (NPs), termed as MMVs/RPNPs, for targeted AS therapy. In this work, we demonstrated that ginsenoside Rb1 can coassemble with probucol without excipients to form stable carrier-free NPs, termed RPNPs. To impart the specific targeting property to atherosclerotic sites, macrophage microvesicles (MMVs) were utilized to coat the RPNPs to obtain the MMVs/RPNPs. Developed MMVs/RPNPs exhibited excellent capabilities in eliminating intracellular ROS, suppressing pro-inflammatory factor secretion, and inhibiting intracellular lipid deposition in vitro. In a mouse model of AS, MMVs/RPNPs efficiently accumulated at atherosclerotic sites following intravenous injection and effectively retarded atherosclerotic plaque formation through synergistic effects of antioxidative stress, anti-inflammation, and inhibition of lipid deposition. Additionally, MMVs/RPNPs did not cause any adverse effects with long-term treatment. Our work presents simple, effective, and safe NPs against AS and underscores the potential of the "integration of Chinese and Western medicine" strategy for treating other cardio-cerebrovascular diseases.