Gold Nanoparticles Inhibit VEGF₁₆₅-Induced Migration and Tube Formation of Endothelial Cells via the Akt Pathway

Abstract

The early stages of angiogenesis can be divided into three steps: endothelial cell proliferation, migration, and tube formation. Vascular endothelial growth factor (VEGF) is considered the most important proangiogenic factor; in particular, VEGF165 plays a critical role in angiogenesis. Here, we evaluated whether gold nanoparticles (AuNPs) could inhibit the VEGF165-induced human umbilical vein endothelial cell (HUVEC) migration and tube formation. AuNPs and VEGF165 were coincubated overnight at 4°C, after which the effects on cell migration and tube formation were assessed. Cell migration was assessed using a modified wound-healing assay and a transwell chamber assay; tube formation was assessed using a capillary-like tube formation assay and a chick chorioallantoic membrane (CAM) assay. We additionally detected the cell surface morphology and ultrastructure using atomic force microscopy (AFM). Furthermore, Akt phosphorylation downstream of VEGFR-2/PI3K in HUVECs was determined in a Western blot analysis. Our study demonstrated that AuNPs significantly inhibited VEGF165-induced HUVEC migration and tube formation by affecting the cell surface ultrastructure, cytoskeleton and might have inhibited angiogenesis via the Akt pathway.

Enzyme-responsive nanocomposites for wound infection prophylaxis in burn management: in vitro evaluation of their compatibility with healing processes

“…26 Pan et al demonstrated that gold NP inhibited HUVEC VEGF165-induced migration and tube formation. 27 On the contrary, neither HYA-PHMB-NC nor PLLA-OCT-NP used in the present studies exhibited any effect on the formation of microcapillary-like structures in the NP-treated co-cultures compared to the untreated co-culture. Thus, angiogenesis, one of the most important factors in the wound healing process, is not influenced by the presence of the nanocompounds, further demonstrating their high tissue compatibility.…”

Gold nanoparticles attenuate metastasis by tumor vasculature normalization and epithelial–mesenchymal transition inhibition

“…13 Our previous studies showed that monotherapy by AuNPs reduced angiogenesis in liver tumors 14 and inhibited VEGF165-induced human umbilical vein endothelial cell (HUVEC) migration and tube formation via the Akt pathway. 15,16 In this study, we aimed to investigate the mechanism of AuNPs in reducing melanoma lung metastasis. Immunofluorescence and immunohistochemistry were carried out to evaluate the vascular morphology, perfusion, permeability and hypoxia in tumors.…”

Metal Nanomaterial Toxicity Variations Within the Vascular System

“…Recent toxicological studies with cell cultures have shown the ability of AuNP to decrease cell viability and proliferation of microvascular endothelial cells (61). Similarly, human umbilical vein endothelial cells exposed to AuNP presented decreased levels of vascular endothelium growth factor (VEGF) (62). VEGF, a major angiogenic factor, also promotes endothelial cell migration and proliferation and may initiate the signaling cascade leading to nitric oxide (NO) production (63).…”

“…It is noteworthy that modulation of VEGF signaling is a recurring theme in the antiangiogenic effects of metallic ENM. Increasing evidence suggests that this effect may occur due to inhibition of phosphorylation of associated downstream effector molecules including Src (83) and Akt (62), which could lead to increased endothelial cells apoptosis (84), impaired hematopoietic cell development, survival, differentiation, and migration (85–87) as well as aberrant vasculogenesis and heart development in prenatally exposed subjects (87). …”