Micellar and structural stability of nanoscale amphiphilic polymers: Implications for anti-atherosclerotic bioactivity

Abstract

Atherosclerosis, a leading cause of mortality in developed countries, is characterized by the buildup of oxidized low-density lipoprotein (oxLDL) within the vascular intima, unregulated oxLDL uptake by macrophages, and ensuing formation of arterial plaque. Amphiphilic polymers (AMPs) comprised of a branched hydrophobic domain and a hydrophilic poly(ethylene glycol) (PEG) tail have shown promising anti-atherogenic effects through direct inhibition of oxLDL uptake by macrophages. In this study, five AMPs with controlled variations were evaluated for their micellar and structural stability in the presence of serum and lipase, respectively, to develop underlying structure-atheroprotective activity relations. In parallel, molecular dynamics simulations were performed to explore the AMP conformational preferences within an aqueous environment. Notably, AMPs with ether linkages between the hydrophobic arms and sugar backbones demonstrated enhanced degradation stability and storage stability, and also elicited enhanced anti-atherogenic bioactivity. Additionally, AMPs with increased hydrophobicity elicited increased atheroprotective bioactivity in the presence of serum. These studies provide key insights for designing more serum-stable polymeric micelles as prospective cardiovascular nanotherapies.

Nanomedicines for dysfunctional macrophage-associated diseases

“…Based on the vital roles of macrophages during progression of atherosclerosis, the following aspects may be considered as potential therapeutic targets to modulate function of macrophages [18, 149–152] to prevent atherosclerosis development: 1) inhibition of leukocyte adhesion [96, 153]; 2) inhibition of LDL oxidation to retard macrophage activation, for instance, use of angiotensin-converting enzyme (ACE) inhibitors to increase the resistance of circulating LDL to oxidation and reduce the development of atherosclerosis in ApoE −− mice independently out of their blood pressure-lowering effects [154, 155]; 3) suppression of macrophage scavenger receptor activities to reduce the uptake of oxLDL, thus preventing foam cell formation [97, 156], and 4) regulation of cholesterol homeostasis in macrophages, for example, reduction of cholesterol ester accumulation and enhancement of cholesterol ester efflux from macrophage within plaques [157, 158]. …”

Self-assembling peptide-based building blocks in medical applications

“…Advantages of micelle-based peptide delivery systems are (i) delivery of a high concentration of peptide to its target (60–90% of the introduced concentration) [37], (ii) stabilization of peptide secondary structure (e.g. α-helices) [38,39], (iii) protection from proteolytic degradation [40,41], (iv) modular building potential to target malignant cells, and (v) the ability to load with multiple different amphiphiles directed at non-redundant protein-protein interaction (PPI) targets. Importantly, these compounds can also be targeted to cells using extracellular targeting ligands, receptor-specific peptides, or antibodies.…”

SCR Tail Gas Treatment of Marine Diesel Engine based on Optimization of Catalyst Structure

“…Diesel engine emissions of carbon monoxide and carbon oxygen compound CO CH gasoline engine is relatively much less, but NOX emissions and gasoline engine in the same order of magnitude, particle emission of PM to several times or more higher than the [1,2] gasoline engine, the emission control of NOX diesel engine is the key and PM (including soot). The emission of diesel engine and is an important source of pollution of the atmosphere, is considered to have high carcinogenicity and has become the main pollution source of suspended particles in the urban air, except for NOX induced human nervous and respiratory disorders are caused by acid rain and photochemical smog formation arch-criminal of a [3], however, the diesel engine emissions and NOX PM is not like the gasoline engine emissions of pollutants that can be effectively solved by using three way catalytic converter, the main reason is the high oxygen content in diesel exhaust, makes use of NOX to restore the reductive reaction difficult, engine exhaust and exhaust temperature of diesel engine was also lower than that of the gasoline engine, is not conducive to the post processing device in catalyst efficient [4]. As people put more emphasis on environmental protection, pollution of diesel vehicles have become more and more prominent, the heavy-duty diesel vehicles is particularly significant, data show that although heavy diesel vehicles accounted for about 15% of the total motor vehicle, but the NOX and PM emissions accounted for more than 60% of the total emissions of motor vehicles.…”