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

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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 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.

Original languageEnglish
JournalACS Applied Nano Materials
Volume4
Issue number4
Pages (from-to)4077-4091
Number of pages15
ISSN2574-0970
DOIs
Publication statusPublished - 2021

Bibliographical note

Publisher Copyright:
© 2021 American Chemical Society.

    Research areas

  • atherosclerosis, biomimetic models, endothelial dysfunction, inflammatory mediators, nanoparticles, VCAM-1

ID: 306680986