Detection and treatment of atherosclerosis using nanoparticles

Abstract

Atherosclerosis is the key pathogenesis of cardiovascular disease, which is a silent killer and a leading cause of death in the United States. Atherosclerosis starts with the adhesion of inflammatory monocytes on the activated endothelial cells in response to inflammatory stimuli. These monocytes can further migrate into the intimal layer of the blood vessel where they are differentiate into macrophages, which take up oxidized low-density lipoproteins and release inflammatory factors to amplify the local inflammatory response. After accumulation of cholesterol, the lipid-laden macrophages are transformed into foam cells, the hallmark of the early stage of atherosclerosis. Foam cells can die from apoptosis or necrosis, the intracellular lipid is deposed in the artery wall forming lesions. The angiogenesis for nurturing cells is enhanced during lesion development. Proteases released from macrophages, foam cells and other cells degrade the fibrous cap of the lesion, resulting in rupture of the lesion and subsequent thrombus formation. Thrombi can block blood circulation, which represents a major cause of acute heart events and stroke. There are generally no symptoms in the early stages of atherosclerosis. Current detection techniques cannot easily, safely and effectively detect the lesions in the early stages, nor can they characterize the lesion feature such as the vulnerability. While the available therapeutic modalities cannot target specific molecules, cells, and processes in the lesions, nanoparticles appear to have a promising potential in improving atherosclerosis detection and treatment via targeting the intimal macrophages, foam cells, endothelial cells, angiogenesis, proteolysis, apoptosis, and thrombosis. Indeed, many nanoparticles have been developed in improving blood lipid profile and decreasing inflammatory response for enhancing therapeutic efficacy of drugs and decreasing their side effects.

Biomimetic Nanotherapies: Red Blood Cell Based Core–Shell Structured Nanocomplexes for Atherosclerosis Management

“…Moreover, no obvious difference in the organ index of heart, liver, spleen, lung, and kidney was observed, suggesting no significant toxicity to the main organs ( Figure 8B). 2019, 6,1900172 indicated that the functions of the liver and kidney were not impaired by the treatment (Figure 8C-F). In addition, the blood biochemical assays of alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (CREA), and blood urea nitrogen (UREA) were at normal levels, which Adv.…”

“…However, when compared with DiD@PLGA, phagocytosis of RBC/DiD@PLGA by macrophages was noticeably reduced. 2019, 6,1900172 phagocytosis. However, the internalization signal of RBC/DiD@PLGA was significantly lower than that of DiD@PLGA, as evidenced by 1.6-, 2.6-, 3.3-, and 2.9-fold decreases at 1, 2, 4, and 8 h incubation, respectively ( Figure 3F).…”

“…The disease is highly prevalent worldwide and is the leading cause of morbidity and mortality in industrialized countries. [5,6] Although surgical interventions (e.g., stenting) are effective for the treatment of advanced atherosclerosis, such procedures are associated with side effects such as restenosis and late stent thrombosis, which hampers the long-term success of surgical intervention. [3,4] Unfortunately, general oral medication is limited to the treatment of early stage atherosclerosis.…”

Multimodality Molecular Imaging of Cardiovascular Disease Based on Nanoprobes

“…Nowadays, lots of literatures report the possibility of multimodality molecular imaging using nanoprobes, which supports the notion that clinical translation of this technology will be feasible in the near future [7,9,10]. Hence, the purpose of this review is to provide readers with a current update of multimodality molecular imaging of cardiovascular disease based on nanoprobes, which focus on six important aspects of cardiovascular diseases, including atherosclerosis, thrombosis, myocardial infarction and postinfarction remodeling, angiogenesis, apoptosis and cardiac stem cell-based therapy.…”

Polymeric Nanomicelles: A Potential Hazard for the Cardiovascular System?

“…As more polymer nanomicelles have been recently proposed for atherosclerosis detection and treatment via targeting the intimal macrophages, foam cells and endothelial cells [20], one would expect that internalization of PMs into atherosclerotic plaques could possibly alter either plaque architecture or composition, thereby increase or decrease in PSS. However increased PSS levels may be a principal mechanism through which plaques rupture, resulting in thrombosis and sudden ischemic clinical events.…”