TITANIUM DIOXIDE NANOMATERIALS EFFECTS ON ENDOTHELIAL CELL BARRIER INTEGRITY: A CASE STUDY OF NANOMATERIALS INTERACTION WITH BIOLOGICAL SYSTEM

Abstract

Blood vessels are the most common conduits in human body which were lined with a single cell layer of endothelial cells (ECs) forming a barrier that regulate the exchange between the blood stream and the surrounding tissue. This makes ECs to be the most likely cells to be encountered by the circulating nanomaterials (NMs) in human body. Here, TiO2 NMs was observed to induce intercellular gaps between adjoining ECs which we coined as nanomaterials induced endothelial cells leakiness (NanoEL). The NanoEL was initiated with the physical interaction of TiO2 NMs with endothelial cells? adherens junction protein, VE-cadherin, which responsible to maintain the integrity of ECs barrier. This interaction led to the disruption of VE-cadherin homophilic interactions and activated an aberrant downstream signal transduction which eventually brought about the cell retraction. Validation in in vivo showed that subcutaneous injection of TiO2 NMs to cause leakiness in the surrounding blood vessels of the mouse. In addition, TiO2 NMs induced blood vessel leakiness promoted the melanoma-to-lung metastasis both in acute and sub-chronic exposure scenario. Overall, our findings uncovered a new toxic effect that is non-cytotoxic but profoundly changes the normal functioning of endothelial cells.