Platinum-cerium bimetallic nano-raspberry for atherosclerosis treatment via synergistic foam cell inhibition and P2Y12 targeted antiplatelet aggregation

Abstract

Massive platelet accumulation and foam cell production are critical in the development of atherosclerotic plaques. Although cardiovascular drugs can provide some relief from atherosclerotic disease, however, the efficacy is limited by first-pass and adverse effects. Herein, we designed a raspberry-liked platinum (Pt) and cerium (Ce) bimetallic nanostructures (PtCe NRs) with ticagrelor loading and PEGylation (DSPE-PEG2000-Ticagrelor-PtCe NRs, DPTP NRs), to weaken the plaques for atherosclerosis treatment via synergistic foam cell inhibition and antiplatelet aggregation. On one hand, the high surface roughness and area of the raspberry shaped structure endowed the bimetallic material amplified reactive oxygen species (ROS) scavenging activity to reduce the production of oxidized low-density lipoproteins in plaques, thus inhibiting the formation of foam cells. On the other hand, ticagrelor could act on the P2Y12 receptor in a non-competitive inhibitory manner to activate the P2Y12-ADCY-cAMP/p-VASP pathway, thereby restraining the massive platelets aggregation and preventing further plaque expansion. After 3 months treatment, the area of atherosclerotic lesions was significantly controlled in high fat diet-fed ApoE−/− mice. Besides, there was no obvious side effects during the treatment. These results demonstrated that DPTP NRs exhibited potential protective function for preventing atherosclerosis progression.