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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 …