Targeting Inflammation With Nanosized Drug Delivery Platforms in Cardiovascular Diseases: Immune Cell Modulation in Atherosclerosis

Abstract

Atherosclerosis (AS) is a disorder of large and medium-sized arteries; it consists in the formation of lipid-rich plaques in the intima and inner media, whose pathophysiology is mostly driven by inflammation. Currently available interventions and therapies for treating atherosclerosis are not always completely effective; side effects associated with treatments, mainly caused by immunodepression for anti-inflammatory molecules, limit the systemic administration of these and other drugs. Given the high degree of freedom in the design of nanoconstructs, in the last decades researchers have put high effort in the development of nanoparticles (NPs) formulations specifically designed for either drug delivery, visualization of atherosclerotic plaques, or possibly the combination of both these and other functionalities. Here we will present the state of the art of these subjects, the knowledge of which is necessary to rationally address the use of NPs for prevention, diagnosis, and/or treatment of AS. We will analyse the work that has been done on: (a) understanding the role of the immune system and inflammation in cardiovascular diseases, (b) the pathological and biochemical principles in atherosclerotic plaque formation, (c) the latest advances in the use of NPs for the recognition and treatment of cardiovascular diseases, (d) the cellular and animal models useful to study the interactions of NPs with the immune system cells.

Nanomaterials as Novel Cardiovascular Theranostics

“…Atherosclerosis refers to the pathophysiological conditions where the medium and large arteries are significantly affected due to spatial deposition of various materials such as lipoproteins (particularly cholesterol), immune cells (circulating monocytes), proinflammatory factors (i.e., macrophages and T-cells), degraded extracellular matrix components and necrotic products. Atherosclerosis is considered to be the primary cause of chronic CVDs, including coronary heart disease, cerebrovascular disease, and peripheral arterial disease [ 38 , 39 , 40 ]. Atherosclerosis is characterized by a series of physiological events, including endothelial dysfunction, inflammatory responses, cell proliferation, lipoprotein deposition, vascular remodeling, and finally, plaque formation [ 41 ].…”

Promising Directions in Atherosclerosis Treatment Based on Epigenetic Regulation Using MicroRNAs and Long Noncoding RNAs

“…Nanoparticles can be used as visualization tools to detect vulnerable atherosclerotic plaques; similar theranostic strategies have already demonstrated the potential for identifying and treating other diseases (including cancer and neurodegenerative disorders) using a variety of imaging methods, including optical imaging, magnetic resonance imaging (MRI), ultrasound and photoacoustics, computed tomography (CT), and nuclear imaging based on single-photon and positron emission tomography [140].…”

The Therapeutic Potential of Nanoparticles to Reduce Inflammation in Atherosclerosis

“…In a clinical trial, treatment inhibiting this pathway with a monoclonal antibody against IL-1β (canakinumab) was investigated with promising results [17,18]. Another anti-inflammatory drug, methotrexate (MTX), which is used as anti-inflammatory drug in autoimmune inflammatory disorders, was suggested to decrease the risk of cardiovascular diseases in subjects who were in a prolonged inflammatory state [19,20]. MTX has also been shown to decrease macrophage recruitment to the vessel wall and to have beneficially effects on atherogenesis in experimental animals [21].…”

“…Incorporation of antibodies such as CD11b and anti-VCAM1, or molecules such as dextran and mannose in theranostic agents for the targeting of macrophages in the plaque has also been reported [36]. Some similar approaches, using imaging techniques for featuring components of atherogenesis, such as magnetic resonance imaging (MRI), optical imaging (OI), ultrasound and photoacoustic (US-PA), nuclear imaging based on single photon and positron emission tomography (SPECT, PET), and computed tomography (CT) are already under investigation [19,36,37,38,39,40]. Although the specificity of nanoparticle targeting has not been fully described, a number of suggestions has been developed.…”