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Proteomics. 2019 Jan 11:e1800228. doi: 10.1002/pmic.201800228. [Epub ahead of print]

Proteomic Analysis of Endothelial Cells Exposed to Ultrasmall Nanoparticles Reveals Disruption in Paracellular and Transcellular Transport.

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Department of Clinical and Experimental Medicine, Cell Biology, Faculty of Medicine, Linköping University, Linköping, Sweden.
Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.
IKERBASQUE, Basque Foundation for Science, Departments of Physiology, Faculty of Medicine and Dentistry, University of the Basque Country, Leioa, Spain.


The large interactive surfaces of nanoparticles increase the opportunities to develop nanoparticles for vascular targeting. Proteomic analysis of endothelial cells exposed to nanoparticles reveals the cellular response and turns the focus into the impairment of the endothelial permeability. Here, we combined quantitative proteomics and transcriptome sequencing to evaluate the effects of exposure to sub-lethal concentrations of TiO2 -USNPs and TiO2 -NPs on human dermal microvascular endothelial cells. Endothelial cells react to preserve the semi-permeable properties that are essential for vascular tissue fluid homeostasis, vascular development and angiogenesis. The main impact of the exposure was alteration of functional complexes involved in cell adhesion, vesicular transport and cytoskeletal structure. Those are the core cellular structures that are linked to the permeability and the integrity of the endothelial tissue. Moreover, the extracellular proteins uptake with the nanoparticle into the endothelial cell, escape the lysosomal degradation pathway. These findings improve our understanding of the interaction of nanoparticles with endothelial cell. The effects of the studied nanoparticles modulating cell-cell adhesion and vesicular transport could help to evaluate the distribution of nanoparticles via intravenous administration. This article is protected by copyright. All rights reserved.


RNA-seq; endothelial cells; nanoparticles; paracellular; proteomics; transcellular transport; ultrasmall nanoparticles


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