Vascular Inflammation: A Novel Access Route for Nanomedicine

Abstract

Despite an improved understanding of its pathophysiology and a wide range of new treatments, cardiovascular disease (CVD) remains a serious public health issue and the number one cause of mortality in the United States. Conditions that promote chronic systemic inflammation, such as obesity, cancer, and autoimmune and infectious diseases, are now known to play an important role in promoting CVD by inducing the expression of endothelial adhesion molecules and chemokines; these in turn promote leukocyte adherence and infiltration, which initiates and spurs the progression of CVD. In response to this new understanding, researchers are evaluating the potential cardiovascular benefits of new-generation therapies based on endogenous molecules with anti-inflammatory properties. Similarly, targeted approaches that leverage the phenotypic differences between non-inflamed and inflamed endothelia have the potential to selectively deliver therapeutics and decrease the morbidity and mortality of CVD patients. In this review, we discuss the role of inflammation in CVD and explore the therapeutic potential of targeting inflamed vasculature through conventional and biomimetic approaches.

Biomimetic nanoparticles with enhanced affinity towards activated endothelium as versatile tools for theranostic drug delivery

“…To expand on the inflammatory recognition of leukosomes, we explored their ability to recognize and target an additional site of inflammation: intimal lesions in a hypercholesterolemic animal. Atherosclerosis is an inflammatory disease, the cellular interactions of which share common characteristics with other chronic inflammatory diseases 2 , 66 . Atherosclerosis is characterized by early changes in the endothelium.…”

“…However, chronic inflammation can lead to multiple pathologies including atherosclerosis, cancer, inflammatory bowel syndrome, and pulmonary diseases 1 . Vascular inflammation, which occurs in the early stages of these diseases, begins with activation of the endothelium in response to hemodynamic, humoral, metabolic, or pathological challenges 2 . Under these conditions, the endothelium begins to express molecules such as vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and selectins 3 , 4 .…”

“…Following systemic administration, NPs encounter several physical and biological barriers that impede their successful delivery to tumors 9 . The endothelium is a significant barrier for all systemically administered agents and functions to restrict access to NPs unless specific conditions are present (e.g., activated endothelium) 2 . In addition, the mononuclear phagocyte system (MPS) recognizes NPs as foreign and removes them from circulation, greatly reducing the amount of NP that can reach its target 10 .…”

Personalized protein corona on nanoparticles and its clinical implications

“…Moreover, many NPs are conceived for intravenous injection and are directly exposed to the vasculature. This can cause vascular inflammation, the formation of atherosclerotic plaques, and oxidative stress, 81–84 demonstrating the need for a better understanding of the cardiovascular toxicity induced by NPs. PCs were obtained by incubating magnetite iron oxide NPs (Fe3O4) with normal/healthy and lipid-rich rat serum.…”

Nanomedicine in rheumatology: A new field in the diagnosis and therapy of rheumatic diseases

“…In response to this new understanding, new-generation therapies based on endogenous molecules with anti-inflammatory properties are in progress. This target-to-treat approach that leverages the phenotypic differences between non-inflamed and inflamed endothelia have the potential to selectively deliver therapeutics and reduce the morbidity and mortality of CVD patients [16].…”