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 Fe 3 O 4 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 T 2 * 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.

Advances in Nanomaterials for Injured Heart Repair

“…Infiltrating monocytes differentiate locally into macrophages, which can further release superoxides, hydroxyl radicals, and hydrogen peroxide to oxidize LDL and absorb a large amount of ox-LDL, resulting in the formation of foam cells. The continuous accumulation of foam cells induces fatty striations on the arterial wall, leading to the development of AS ( Ye et al, 2019 ). Meanwhile, the recruited macrophagesalso can secrete a variety of mediators, such as interleukin-1 (IL-1), platelet–derived growth factor and transforming growth factor (TGF-α), which participate in the inflammation and immune responses and significantly accelerate the proliferation of VSMCs.…”

Current Research Landscape of Marine-Derived Anti-Atherosclerotic Substances

“…Ye et al successfully fabricated nanoparticles targeting SR-A, which is potential for the treatment of atherosclerosis. Moreover, in a vitro model of atherosclerotic plaque, it has shown the fact that the nanoparticles selectively accumulated at sites with high SR-A expression and the use of low intensity focused ultrasound-induced phase transition improves the condition of vessels in vivo [115]. Li et al conjugated hydroxybutyl chitosan (HBC) to anti-CD133 antibody to prepare a CD133 antibody-coated stent, which has shown the ability to decrease intimal hyperplasia and reduce restenosis in contrast with bare stents, which suggests that the stents of the CD133 antibody coat may contribute to the treatment of AS [116].…”

Iron Oxide Nanoparticles as Imaging and Therapeutic Agents for Atherosclerosis

“…Collagen IV is abundantly expressed on the surface of plaques and one research group achieved collagen IV targeted delivery by conjugating C11, a peptide specific for collagen IV, to the surface of iron oxide-paclitaxel-polymer-lipid nanoparticles. 64 Their nanoparticles accumulated in collagen IV containing Matrigel and macrophages in vitro in greater concentrations than untargeted nanoparticles and were shown to release the drug under these conditions. Their nanoparticles also showed enhanced in vivo MRI contrast and therapeutic efficacy in rabbits.…”