Lanthanide Hydroxide Nanoparticles Induce Angiogenesis via ROS-Sensitive Signaling.

Recent studies suggest that the nanorods consisting of europium hydroxide could promote angiogenesis. In this study, it is sought to determine if additional types of nanoparticles are capable of enhancing angiogenesis and in addition, understand the underlying mechanisms. For this reason, a method is employed that combines a high throughput in vitro cell based screen coupled with an in vivo validation using vascular specific green fluorescent protein reporter transgenic zebrafish for examining proangiogenesis activity. After screening multiple types of nanoparticles, it is discovered that four of them, Eu(III) (OH)3 rods (Eu rods), Eu(III) (OH)3 spheres (Eu spheres), Tb(III) (OH)3 rods (Tb rods), and Tb(III) (OH)3 spheres (Tb spheres), are the most effective in promoting angiogenesis. It is also showed that ionic forms of europium nitrate [Eu(NO3 )3 ] (Eu) and terbium nitrate [Tb(NO3 )3 ] (Tb), the two lanthanide elements for these four nanoparticles, are also capable of enhancing angiogenesis. However, this effect is further enhanced by nanoparticle synthesis. Finally, it is demonstrated that reactive oxygen species H2 O2 is a key factor in the process of proangiogenesis by lanthanide elemental nanoparticles.