ABSTRACT
As discussed in previous chapters, vascular-targeting via endothelial cell (EC)-expressed molecules has potential for diagnostic and therapeutic applications in several human diseases, particularly in many cancers and cardiovascular diseases. However, the capacity to localize drug therapy to diseased vasculature while avoiding healthy vessels would depend on the uniqueness of the targeted receptors’ expression to the disease state or tissue and a precise match between the targeting ligands on the delivery
1Department of Chemical and Biomolecular Engineering, University of Illinois, 600 S. Mathews, RAL 4, C3, Urbana, Illinois 61801. Email: rbhuang@illinois.edu 2Department of Chemical Engineering, University of Michigan, 2300 Hayward Street, 3074 H.H. Dow, Ann Arbor, Michigan 48109. *Corresponding author: lolaa@umich.edu
vehicle and their endothelial-based receptors. This is particularly the case for targeting endothelial cell surface-expressed molecules associated with chronic infl ammation, which is known to be associated with a number of disease pathologies. Here, vascular-targeted carriers must be able to successfully differentiate protein expression patterns observed during chronic infl ammation under disease conditions from expression patterns associated with acute infl ammation of the healthy endothelium. With ethical practices and government regulations precluding the use of human in vivo models and the fact that endothelial response in animal models are known to not translate well to human physiology, researchers have focused on developing in vitro models of human infl ammatory response. To this end, current in vitro models have attempted to mimic relevant endothelial cell infl ammatory response in health and in disease; however, many fail to simulate the actual physiological conditions under which infl ammation occurs. The bulk of the literature is represented by evaluation of endothelial cell protein expression in static culture, typically on glass or plastic substrates. While these works have been critical in elucidating the roles of different chemical cues in eliciting protein expression in many physiological and pathological processes, these studies often fail to encompass the true in vivo environment under which such endothelial activation occurs.
