Engineering Nanomaterials to Address Cell-Mediated Inflammation in Atherosclerosis

Atherosclerosis is an inflammatory disorder with a pathophysiology driven by both innate and adaptive immunity and a primary cause of cardiovascular disease (CVD) worldwide. Vascular inflammation and accumulation of foam cells and their products induce maturation of atheromas, or plaques, which can rupture by metalloprotease action, leading to ischemic stroke or myocardial infarction. Diverse immune cell populations participate in all stages of plaque maturation, many of which directly influence plaque stability and rupture via inflammatory mechanisms. Current clinical treatments for atherosclerosis focus on lowering serum levels of low-density lipoprotein (LDL) using therapeutics such as statins, administration of antithrombotic drugs, and surgical intervention. Strategies that address cell-mediated inflammation in atherosclerosis are lacking and consequently have recently become an area of considerable research focus. Nanomaterials have emerged as highly advantageous tools for these studies, as they can be engineered to target specific inflammatory cell populations, deliver therapeutics of wide-ranging solubilities and enhance analytical methods that include imaging and proteomics. Furthermore, the highly phagocytic nature of antigen-presenting cells (APCs), a diverse cell population central to the initiation of immune responses and inflammation, make them particularly amenable to targeting and modulation by nanoscale particulates. Nanomaterials have therefore become essential components of vaccine formulations and treatments for inflammation-driven pathologies like autoimmunity, and present novel opportunities for immunotherapeutic treatments of CVD. Here, we review recent progress in the design and use of nanomaterials for therapeutic assessment and treatment of atherosclerosis. We will focus on promising new approaches that utilize nanomaterials for cell-specific imaging, gene therapy, and immunomodulation. Lay Summary CVD continues to be the leading cause of death in the developed world and is a considerable economic burden. The underlying mechanism of most CVD is atherosclerosis, an inflammatory condition characterized by cellularly complex plaque deposits within arterial vessel walls. Therapies that adequately address cell-mediated inflammation and diagnostic tools for early detection of vulnerable plaques are critical weaknesses of current clinical strategies for treating CVD, and nanomaterials have been engineered to uniquely address both of these needs. Here, we review recent progress in the use of nanomaterials designed to enhance imaging and therapeutic intervention of atherosclerotic inflammation.