Low-dose albumin-coated gold nanorods induce intercellular gaps on vascular endothelium by causing the contraction of cytoskeletal actin.

Cytotoxicity of nanoparticles, typically evaluated by biochemical-based assays, often overlook the cellular biophysical properties such as cell morphology and cytoskeletal actin, which could serve as more sensitive indicators for cytotoxicity. Here, we demonstrate that low-dose albumin-coated gold nanorods (HSA@AuNRs), although being considered noncytotoxic in multiple biochemical assays, can induce intercellular gaps and enhance the paracellular permeability between human aortic endothelial cells (HAECs). The formation of intercellular gaps can be attributed to the changed cell morphology and cytoskeletal actin structures, as validated at the monolayer and single cell levels using fluorescence staining, atomic force microscopy, and super-resolution imaging. Molecular mechanistic study shows the caveolae-mediated endocytosis of HSA@AuNRs induces the calcium influx and activates actomyosin contraction in HAECs. Considering the important roles of endothelial integrity/dysfunction in various physiological/pathological conditions, this work suggests a potential adverse effect of albumin-coated gold nanorods on the cardiovascular system. On the other hand, this work also offers a feasible way to modulate the endothelial permeability, thus promoting drug and nanoparticle delivery across the endothelium.