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

Abstract

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.

Silica nanomaterials induce organ injuries by Ca2+-ROS-initiated disruption of the endothelial barrier and triggering intravascular coagulation

“…We showed that SiNPs induced F-actin re-assembly in HUVECs. Actin filaments remodeling has been observed in titanium dioxide nanoparticles and gold nanoparticles that induced endothelial barrier destruction [15,17]. Actin microfilaments can interact with endothelial adhesion structures and cooperatively regulate the cell shape.…”

“…Leong's group [15][16][17][18] demonstrated the toxicity of inorganic nanoparticles to vascular endothelial (VE)-cadherin, a critical adherens junction protein which participates in the integrity of endothelial barrier/permeability, in the cytotoxicity of inorganic nanoparticles.…”

“…Titanium dioxide nanomaterials induced endothelial leakiness [15] and accelerated both intravasation and extravasation of breast cancer cells by disrupting the homophilic interaction of VE-cadherin [16]. Gold nanoparticles induced endothelial leakiness by VE-cadherin phosphorylation and expression downregulation [17]. Mesoporous SiNPs directly increased endothelial permeability by perturbing VE-cadherin-based endothelial cellcell adhesion in a gravitational way [18].…”

Cell Membrane Nanotherapeutics: From Synthesis to Applications Emerging Tools for Personalized Cancer Therapy

“…The NanoEL concept advocates the use of nanotechnology to increase endothelial leakiness. [ 173–180 ] Endothelial leakiness is critical in determining accessibility of drugs and nanomaterials to target sites as current practices in pharmaceutical agents delivery is intravenous. [ 181,182 ] If the addressing and accessibility issue to the target site can be solved through combining cell membrane targeting concepts with NanoEL principles, there will be logically higher localized dose delivered to a specific target site.…”

Effect of the hyaluronic acid‐poloxamer hydrogel on skin‐wound healing: in vitro and in vivo studies

“…The first two aspects, coagulation and infection prevention, apply to early skin‐wound healing . Growth factors promote subsequent germinal layer cell division and neovascularization, and various types of nano‐material such as gold and silver nanoparticles have been used to promote granulation tissue differentiation . However, several issues around skin‐wound healing are not fully resolved: (a) hemostatic and anti‐infective materials are often ineffective at promoting wound healing; (b) growth factors can induce hyperblastosis or tumorigenesis; (c) although remarkable effects of nano‐materials have been reported, gold or silver nanoparticles may remain in scar tissue for a long time .…”