Effect of Nanoparticle Biophysicochemical Properties on Binding and Transport across Cardiovascular Endothelial Dysfunction Models

Cardiovascular disease remains the number one cause of mortality and morbidity worldwide and includes atherosclerosis, which presents as a deadly and chronic inflammatory disease. The initial pathological factor in atherosclerosis is a dysfunctional endothelium (Dys-En), which results in enhanced permeability of the endothelium and enhanced expression of adhesion molecules such as vascular cell adhesion molecule 1 (VCAM-1), among others. Nanomedicines represent a growing arsenal of novel therapeutics aimed at treating atherosclerosis; however, nanoparticle (NP) interactions as a function of their biophysiochemical properties with the Dys-En are not currently well understood. In this study, we investigated targeted NP biophysicochemical properties for maximal VCAM-1 binding and permeability across several Dys-En models that we established using cardiovascular inflammatory mediators. We found that NP size governs permeability and binding, regardless of the type and density of VCAM-1 peptide ligand used. Our results suggest that the design of NPs in the range of 30-60 nm can highly increase permeability and binding across the Dys-En. These findings confirm the importance of in vitro models of Dys-En as a preliminary screening and predictive tool for atherosclerosis NP targeting.