Spontaneous Induced Cascade Targeting Biomimetic Nanoparticles to Inhibit Dendritic Cell Maturation for Ameliorating Atherosclerosis and Magnetic Resonance Imaging.

Abstract

The major fatal factor of cardiovascular disease is atherosclerosis, which is a chronic inflammatory disease featured by immune cell infiltration within arterial plaques. Dendritic cells (DCs) are central stimulators of atherosclerotic inflammation, with mature DCs generating pro-inflammatory signals within plaque lesions and tolerogenic DCs promoting anti-inflammatory cytokine production and regulatory T cell (T_reg) activation. In this work, spontaneous induced cascade targeting biomimetic nanoparticles (MM@HGPBRD) were constructed to target DCs in atherosclerosis plaques to inhibit DC maturation. In vitro and in vivo experiment results showed that the MM@HGPBRD effectively slowed atherosclerosis progression by the synergistic effect of multiple components. The coating macrophage membrane helped the nanoparticles to evade immune clearance and home to the atherosclerotic site. Then, the nanozyme activity of hollow mesoporous Prussian blue (HGPB) produced oxygen to break the membrane and expose DC-SIGN aptamer to realize cascade targeting to DCs and enhance the targeted release of rapamycin (RAPA) to inhibit DC maturation. The whole process regulated the inflammatory and immune microenvironment of atherosclerosis. At the same time, the excellent magnetic resonance imaging (MRI) ability of HGPB favored the MRI of DCs in atherosclerosis plaque. This study provides new avenue for spontaneous induced cascade targeting and modulating DC maturation to improve atherosclerosis inflammation and immune microenvironment.