SR-A-Targeted Phase-Transition Nanoparticles for the Detection and Treatment of Atherosclerotic Vulnerable Plaques.

Abstract

Atherosclerosis is a major cause of sudden death and myocardial infarction, instigated by unstable plaques. Thus, the early detection of unstable plaques and corresponding treatment can improve the prognosis and reduce mortality. In this study, we describe a protocol for the preparation of nanoparticles (NPs) combined with the phase transitional material perfluorohexane (PFH) and with dextran sulfate (DS) targeting class A scavenger receptors (SR-A) for the diagnosis and treatment of atherosclerotic vulnerable plaques. The results showed that the Fe-PFH-poly(lactic- co-glycolic acid) (PLGA)/chitosan (CS)-DS NPs were fabricated successfully, with the ability to undergo phase transition by low-intensity focused ultrasound (LIFU) irradiation to achieve ultrasound imaging; a high carrier rate of Fe3O4 had a good negative enhancement effect on magnetic resonance imaging (MRI). The NPs had a high binding affinity for activated macrophages and could be endocytosed by the macrophages and notably induced apoptosis under LIFU irradiation by an acoustic droplet vaporization effect in vitro. Furthermore, in an ex vivo atherosclerotic plaque model of apolipoprotein E knockout (KO) (apoE-/-) mice induced by high cholesterol, the NPs selectively accumulated at the sites of SR-A expressed on the activated macrophages of the aortic region. This result was also confirmed by MRI in vivo, where the NPs could be targeted to the aortic plaque and reduced the T2* signal. The LIFU-induced phase transition could lead to the apoptosis of macrophages on plaques in vivo. In summary, Fe-PFH-PLGA/CS-DS NPs may be applied as multimodal and multifunctional probes and are expected to enable the specific diagnosis and targeted therapy of vulnerable plaques.