GOLD NANOPARTICLE SIZE, SHAPE AND CHARGE DETERMINE THE EXTENT OF NANOPARTICLE INDUCED ENDOTHELIAL LEAKINESS EFFECT

Abstract

Nanoparticles (NPs) could induce gaps between endothelial cells which we coined as nanoparticles induced endothelial leakiness (NanoEL). It is a novel NP driven effect. Nanoparticle parameters that determine NanoEL are slowly emerging but under intense investigation. In this work, it is proposed that size, shape, and charge differences of NPs determine NanoEL. Au and mesoporous SiO2 NPs are used due to high biocompatibility. We found that only certain size ranges (less than 300 nm) of spherical Au NPs can cause NanoEL by fitting into the adherens junctions between endothelial cells and disrupt VE-Cadherin pairs. Moreover, shapes of Au NPs do not impact NanoEL significantly. Furthermore, negatively charged NPs could be repelled by the negatively charged glycocalyx on plasma membrane until it reaches cell junctions, inducing targeted NanoEL. In addition, tumor therapy could be enhanced during NaonoEL. Eventually, NanoEL may be a feasible and controllable manner for nanomedicines to access tumors.