A Framework of Paracellular Transport via Nanoparticles‐Induced Endothelial Leakiness

Abstract

Nanomaterial‐induced endothelial leakiness (NanoEL) is an interfacial phenomenon denoting the paracellular transport of nanoparticles that is pertinent to nanotoxicology, nanomedicine and biomedical engineering. While the NanoEL phenomenon is complementary to the enhanced permeability and retention effect in terms of their common applicability to delineating the permeability and behavior of nanoparticles in tumoral environments, these two effects significantly differ in scope, origin, and manifestation. In the current study, the descriptors are fully examined of the NanoEL phenomenon elicited by generic citrate‐coated gold nanoparticles (AuNPs) of changing size and concentration, from microscopic gap formation and actin reorganization down to molecular signaling pathways and nanoscale interactions of AuNPs with VE‐cadherin and its intra/extracellular cofactors. Employing synergistic in silico methodologies, for the first time the molecular and statistical mechanics of cadherin pair disruption, especially in response to AuNPs of the smallest size and highest concentration are revealed. This study marks a major advancement toward establishing a comprehensive NanoEL framework for complementing the understanding of the transcytotic pathway and for guiding the design and application of future nanomedicines harnessing the myriad functions of the mammalian vasculature.

Anionic nanoplastic exposure induces endothelial leakiness

“…2d and Supplementary Fig. 7 ) 21 . The derived percentages of gap areas corroborated data from the transwell assay, where endothelial leakiness was more pronounced over time for PS nanoplastic of 0.05 and 0.5 mg/mL.…”

“…Many metal oxide nanoparticles can induce cellular ROS 23 , indirectly leading to endothelial leakiness through cytoskeletal damage 24 . On the other hand, cellular uptake is not necessary for the occurrence of the leakiness 21 . Among the relevant biomarkers, 4-amino-5-(4-methylphenyl)−7-(t-butyl)pyrazolo[3,4-d]-pyrimidine (PP1) is a Src kinase inhibitor that inhibits VE-cadherin phosphorylation 25 , rho-associated protein kinase (ROCK) inhibitor Y-27632 prevents perturbation to the cytoskeletal network 26 , and N-Acetyl-L-cysteine (NAC) inhibits ROS generation.…”

“…Anionic inorganic nanoparticles can migrate to and disrupt the adherens junctions between endothelial cells to induce NanoEL 21 . Interestingly, we observed NanoEL in HUVECs in the presence of polymeric PS nanoplastic.…”

Dynamic Protein Corona of Gold Nanoparticles with an Evolving Morphology

“…Rational design of NPs has previously enabled the control of NanoEL in different cellular and animal model systems, , but little is known about the formation and effect of the protein corona on NanoEL. Furthermore, no data is available about the relationship between a dynamic protein corona and NanoEL.…”

Amino-Functionalized Polystyrene Nano-Plastics Induce Mitochondria Damage in Human Umbilical Vein Endothelial Cells

“…To date, in vitro toxicity studies of nano-plastics have mainly focused on gastrointestinal cells, respiratory tract cells, liver cells, and immunity cells [ 17 , 18 , 19 , 20 ]. Endothelial cells line the lumen of all blood vessels, which play essential roles in nutrition, waste transportation, and cell movement [ 21 ]. The function of endothelial cells affects the blood vessel integrity and is associated with various diseases, such as cancer and inflammation [ 22 ].…”