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In this condition, structural extracellular matrix (ECM) proteins of the aorta wall, elastic fibers and collagen fibers, that impart elasticity and stiffness respectively, are slowly degraded by overexpressed matrix metalloproteinases (MMPs) following an injury stimulus. We are seeking to deliver therapeutics to the AAA wall using polymer nanoparticles (NPs) that are capable of stimulating on\u2010site matrix regeneration and repair. This study aimed to determine how NP shape and size impacts endocytosis and transmigration past the endothelial cell (EC) layer from circulation into the medial layer of the AAA wall. First, rod\u2010shaped NPs were shown to be created based mechanical stretching of PLGA NPs while embedded in a PVA film with longer rod\u2010shaped NPs created based of the degree in which the PVA films are stretched. Live\/dead assay reveals that our PLGA NPs are safe and do not cause cell death. Immunofluorescence staining reveal cytokine activation causes endothelial dysfunction in ECs by increasing expression of inflammatory marker Integrin \u03b1V\u03b23 and decreasing expression of adhesion protein vascular endothelial (VE)\u2010cadherin. We showed this disruption enable greater EC uptake and translocation of NPs. Fluorescence studies demonstrate high endothelial transmigration and endocytosis with rod\u2010shaped NPs in cytokine activated ECs compared to healthy control cells, arguing for the benefits of using higher aspect ratio (AR) NPs for accumulation at the aneurysm site. We also demonstrated that the mechanisms of NP transmigration across an activated EC layer depend on NP AR. These results show the potential of using shape as a modality for enhancing permeation of NPs into the aneurysm wall. These studies are also significance to understanding the mechanisms that are likely engaged by NPs for penetrating the endothelial lining of aneurysmal wall segments.<\/jats:p>","DOI":"10.1002\/jbm.a.37667","type":"journal-article","created":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T07:24:30Z","timestamp":1704785070000},"page":"881-894","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Assessing trans\u2010endothelial transport of nanoparticles for delivery to abdominal aortic aneurysms"],"prefix":"10.1002","volume":"112","author":[{"given":"Jimmy","family":"Yau","sequence":"first","affiliation":[{"name":"Department of Bioengineering Lehigh University  Bethlehem Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patience","family":"Chukwu","sequence":"additional","affiliation":[{"name":"Department of Bioengineering Lehigh University  Bethlehem Pennsylvania 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