Vascular tube formation and angiogenesis induced by polyvinylpyrrolidone-coated silver nanoparticles

Silver nanoparticles (AgNPs) are one of the most commonly used nanomaterials due to their antibacterial properties. In this study, we examined the effects of polyvinylpyrrolidone (PVP)-coated AgNPs (average size 2.3 nm) on angiogenesis in both an in vivo model and an in vitro endothelial cell line, SVEC4-10. Increased angiogenesis was detected around the injection site of AgNP-containing Matrigel in vivo. AgNPs also increased the infiltration of endothelial cells and the hemoglobin (Hb) content in AgNP-Matrigel plugs implanted into mice. AgNPs induced endothelial cell tube formation on growth factor-reduced Matrigel, production of reactive oxygen species (ROS), and production of angiogenic factors, such as vascular endothelial growth factor (VEGF) and nitric oxide (NO), in SVEC4-10 cells. In addition, AgNPs promoted the activation of FAK, Akt, ERK1/2, and p38, which are all involved in VEGF receptor (VEGFR)-mediated signaling. Finally, AgNP-treated tumors caused angiogenesis around tumors in B16F10 melanomas after they were injected into mice, and the Hb concentration in the tumors increased in a concentration-dependent manner with AgNP treatment. Thus, our study suggests that exposure to AgNPs can cause angiogenesis through the production of angiogenic factors.