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.
The kidney is one of the body’s main filtration organs, and hence, opportunity exists for designing nanomedicine that can naturally accumulate in the kidneys for renal diseases. In addition to traditional physiochemical properties for kidney accumulation, such as size and charge, synthesized nanoparticles can be conjugated with targeting ligands which further home the nanocarriers to cell types of interest In this review, we highlight key studies that have shown success in utilizing peptide- or antibody-based ligands in nanoparticles to target the glomerulus, podocytes, or renal tubule cells in the kidney. In addition, other ligand candidates which have shown renal affinity, but have not yet been integrated into a nanoparticle are also presented. These studies can provide insight into the design of novel clinical solutions for improved detection, prevention, and treatment of renal diseases using nanomedicine efforts
Tissue engineering aims to develop scaffolds that are biocompatible and mimic the mechanical and biological properties of the target tissue as closely as possible. Here, we describe the fabrication and characterization of a biodegradable, elastomeric porous scaffold: poly(1,8-octanediol-co-citric acid) (POC) incorporated with nanoscale hydroxyapatite (HA). While this chapter focuses on the scaffold's potential for bone regeneration, POC can also be used in other tissue engineering applications requiring an elastomeric implant. Because of the relative ease with which POC can be synthesized, its mechanical properties can be tailored to mimic the structure and function of the target elastomeric tissue for enhanced tissue regeneration.
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