Therapeutic applications of nanomedicine in metabolic diseases by targeting the endothelium.

The endothelial cells not only constitute the barrier between the blood and interstitial space, but also actively regulate vascular tone, blood flow and the function of adjacent parenchymal cells. The close anatomical relationship between endothelial cells and highly vascularized metabolic organs suggests that the crosstalk between these units is vital for systemic metabolic homeostasis. Here, we review recent studies about the pivotal role of endothelial cells in metabolic diseases. Specifically, we discuss how the dysfunction of endothelial cells directly contributes to the development of insulin resistance, type 2 diabetes mellitus, atherosclerosis and non-alcoholic fatty liver disease via communication with parenchymal cells. Furthermore, although many biological macromolecules have been shown to ameliorate the progression of metabolic diseases by improving endothelial function, the low solubility, poor bioavailability or lack of specificity of these molecules limit their clinical application. Given the advantages in drug delivery of nanomedicine, we focus on summarizing the reports that improving endothelial dysfunction through nanomedicine-based therapies provides an opportunity for preventing metabolic diseases.