Targeting cell adhesion molecules with nanoparticles usingin vivoand flow-basedin vitromodels of atherosclerosis

Abstract

Impact statementAs atherosclerosis remains the leading cause of death, there is an urgent need to develop better tools for treatment of the disease. The ability to improve current treatments relies on enhancing the accuracy of in vitro and in vivo atherosclerotic models. While in vivo models provide all the relevant testing parameters, variability between animals and among models used is a barrier to reproducible results and comparability of NP efficacy. In vitro cultures isolate cells into microenvironments that fail to take into account flow separation and shear stress, which are characteristics of atherosclerotic lesions. Flow-based in vitro models provide more physiologically relevant platforms, bridging the gap between in vivo and 2D in vitro models. This is the first review that presents recent advances regarding endothelial cell-targeting using adhesion molecules in light of in vivo and flow-based in vitro models, providing insights for future development of optimal strategies against atherosclerosis. AbstractAtherosclerosis is a leading cause of death worldwide; in addition to lipid dysfunction, chronic arterial wall inflammation is a key component of atherosclerosis. Techniques that target cell adhesion molecules, which are overexpressed during inflammation, are effective methods to detect and treat atherosclerosis. Specifically, research groups have identified vascular cell adhesion molecule-1, intercellular adhesion molecule-1, platelet endothelial cell adhesion molecule, and selectins (E-selectin and P-selectin) as correlated to atherogenesis. In this review, we discuss recent strategies both in vivo and in vitro that target cell adhesion molecules. First, we discuss peptide-based and antibody (Ab)-based nanoparticles utilized in vivo for diagnostic, therapeutic, and theranostic applications. Second, we discuss flow-based in vitro models that serve to reduce the traditional disadvantages of in vivo studies such as variability, time to develop the disease, and ethical burden, but preserve physiological relevance. The knowledge gained from these targeting studies can be translated into clinical solutions for improved detection, prevention, and treatment of atherosclerosis.

ICAM-1 targeting, intracellular trafficking, and functional activity of polymer nanocarriers coated with a fibrinogen-derived peptide for lysosomal enzyme replacement

“…The literature has described several non-antibody affinity peptides capable of selective binding to ICAM-1, including peptides identified by phage display or derived from the sequence of proteins that can bind to ICAM-1, such as MUC1 mucin core proteins, P(0) CAM, leukocyte functional antigen-1 (LFA-1), and others [38-42]. These peptides were designed and tested mostly in the context of blocking ICAM-1-mediated inflammation and/or cancer metastasis, and some of them also showed potential for use in drug delivery and imaging [20,21-42,43].…”

“…These peptides were designed and tested mostly in the context of blocking ICAM-1-mediated inflammation and/or cancer metastasis, and some of them also showed potential for use in drug delivery and imaging [20,21-42,43]. However, most of these peptides were specifically designed to target human ICAM-1 and their species cross-reactivity for use in laboratory animals is unknown.…”

Synthesis of Monocyte-targeting Peptide Amphiphile Micelles for Imaging of Atherosclerosis

“…Nanoparticles have shown to be an emerging platform for in vivo plaque targeting and diagnostics 18,19,20,21 . In particular, PAMs are advantageous due to their chemical diversity and ability to accommodate a variety of moieties, compositions, sizes, shapes, and surface functionalization 22 .…”

Curcumin suppresses pro-inflammatory adhesion response in Human Umbilical Vein Endothelial Cells

“…Atherosclerosis is correlated to increased expression of adhesion molecules such as ICAM-1, VCAM-1, and E-selectin by vascular endothelium (Chumachenko, Leusova, Kheimets, & Chasova, 2016;Khodabandehlou, Masehi-Lano, Poon, Wang, & Chung, 2017), and inflammatory monocytes recruitment and differentiation into foamy macrophages in nascent plaque (Robbins et al, 2013). Tethering and rolling, the initial steps of monocyte adhesion to the endothelial surface (Michell, Andrews, Woollard, & Chin-Dusting, 2011), appear to depend on the binding of P-and E-selectin with sialofucosylated carbohydrates expressed on leukocytes (Buffone et al, 2013).…”