Synthesis and Characterization of Fucoidan-Chitosan Nanoparticles Targeting P-Selectin for Effective Atherosclerosis Therapy

Abstract

Atherosclerosis is the key pathogenesis of cardiovascular diseases; oxidative stress, which is induced by the generated excess reactive oxygen species (ROS), has been a crucial mechanism underlying this pathology. Nanoparticles (NPs) represent a novel strategy for the development of potential therapies against atherosclerosis, and multifunctional NPs possessing antioxidative capacities hold promise for amelioration of vascular injury caused by ROS and for evading off-target effects; materials that are currently used for NP synthesis often serve as vehicles that do not possess intrinsic biological activities; however, they may affect the surrounding healthy environment due to decomposition of products. Herein, we used nontoxic fucoidan, a sulfated polysaccharide derived from a marine organism, to develop chitosan–fucoidan nanoparticles (CFNs). Then, by binding to P-selectin, an inflammatory adhesion exhibited molecule expression on the endothelial cells and activated platelets, blocking leukocyte recruitment and rolling on platelets and endothelium. CFNs exhibit antioxidant and anti-inflammatory properties. Nevertheless, by now, the application of CFNs for the target delivery regarding therapeutics specific to atherosclerotic plaques is not well investigated. The produced CFNs were physicochemically characterized using transmission electron microscopy (TEM), together with Fourier transform infrared spectroscopy (FTIR). Evaluations of the in vitro antioxidant as well as anti-inflammatory activities exhibited by CFNs were based on the measurement of their ROS scavenging abilities and investigating inflammatory mediator levels. The in vivo pharmacokinetics and binding efficiency of the CFNs to atherosclerotic plaques were also evaluated. The therapeutic effects indicated that CFNs effectively suppressed local oxidative stress and inflammation by targeting P-selectin in atheromatous plaques and thereby preventing the progression of atherosclerosis.

Advances in treatment strategies based on scavenging reactive oxygen species of nanoparticles for atherosclerosis

“…In this experiment, CFNs effectively scavenged hydroxyl radicals and superoxide radicals and inhibited the secretion of inflammatory factors IL-6, IL-1β, and TNF-α in macrophages. A large accumulation of green CFNs in atherosclerotic plaques was observed by fluorescence imaging, confirming their good targeting ability [ 57 ].…”

Oligosaccharides as Potential Therapeutics against Atherosclerosis

“…Furthermore, CFNs intravenously injected into atherosclerotic ApoE −/− mice accumulated in atherosclerotic plaques, subsequently decreasing the average plaque area (by 36.5%), and the necrotic core area, and enhancing the fibrous cap thickness around the plaques, thus stabilising the atherosclerotic plaques. At the same time, long-term CFN treatment did not cause any significant adverse effects on the heart, liver, lungs, spleen, or kidneys, thus confirming its safety [ 33 ]. Together, the in vitro and in vivo results suggested that COS effectively reduced lipid levels, and suppressed local oxidative stress and inflammation, by targeting P-selectin in atheromatous plaques, and modulating the lipid metabolism, thereby preventing the progression of atherosclerosis.…”

Biomaterials-Based Antioxidant Strategies for the Treatment of Oxidative Stress Diseases

“…This modification enabled the NPs to effectively impede leukocyte recruitment and rolling on platelets and endothelium. These NPs were shown to exhibit antioxidant and anti-inflammatory properties in vitro and effectively suppressed local oxidative stress and inflammation in mice [185]. Tempol (SOD mimetic agent) and phenylboronic acid pinacol ester (a hydrogen peroxide-eliminating compound) were encapsulated onto a cyclic polysaccharide β-cyclodextrin NPs.…”