Strategies to enhance nanoparticle - endothelial interactions under flow

Recent years have brought about substantial advances in nanomedical approaches to human diseases. Novel therapeutic and diagnostic nanoparticulate agents can be delivered via several routes, including enteral, transdermal, inhalational, as well as parenteral application. For nanoparticles administered via intravascular route, endothelial cells represent the firstcontact cells and their responses to the candidate nanosystems should be considered before clinical applications. Additionally, a number of drug-delivery nanosystems that target endothelium are currently proposed. It is increasingly evident that the future progress in the treatment of many human maladies, including cardiovascular diseases and cancer, will be closely bound with the development of endothelium-targeting nanosystems. As endothelial cells in circulation are constantly exposed to shear stress, investigating nanoparticle-endothelial interactions under flow conditions is necessary to estimate the cell responses in physiological-like settings. This mini-review focuses on the recently reported studies assessing the uptake of circulating nanoparticles and their biological effects on endothelial cells, and summarizes the targeting approaches to enhance endothelial internalization of nanoparticles under flow conditions.