Gold Nanoparticles Induced Endothelial Leakiness Depends on Particle Size and Endothelial Cell Origin

The endothelium presents a formidable barrier for cancer nanomedicine, as the intravenously introduced nanomedicine needs to leave the blood vessel at the tumor site. Endothelial permeability and retention effect (EPR) is not dependable since it is derived from tumors. Certain nanoparticles with specific characteristics are able to induce micrometer sized gaps between endothelial cells. This effect is called "nanoparticle induced endothelial leakiness" (NanoEL). NanoEL therefore allows the nanotechnology to control access to the tumor even in the absence of any EPR effect. Morever, NanoEL can be applicable to noncancer issues, thereby expanding its usefulness in other subfields of nanomedicine. In this paper, we have shown that Gold (Au) nanoparticles within the range of 10-30 nm are good NanoEL inducing particles. As not all endothelial cells have the same permeability, we found that human mammary endothelial cells and human skin endothelial cells are sensitive to Au induced NanoEL, while human umbilical vein endothelial cells are insensitive, reflective of their innate nature of endothelial permeability. The size window and endothelial cell type sensitivity then helps the nanotechnologists to design future nanoparticles that either exploit NanoEL as a nanotechnology driven strategy to access immature tumors, which do not induce the EPR effect, or avoid NanoEL as a nanotoxic side effect.