Lanthanide Hydroxide Nanoparticles Induce Angiogenesis via ROS-Sensitive Signaling

• Published in: Small (Weinheim an der Bergstrasse, Germany) Vol. 12; no. 32; pp. 4404 - 4411
• Main Authors: Zhao, Haishan, Osborne, Olivia J., Lin, Sijie, Ji, Zhaoxia, Damoiseux, Robert, Wang, Yuqiang, Nel, André E., Lin, Shuo
• Format: Journal Article
• Language: English
• Published: Germany Blackwell Publishing Ltd 01.08.2016; Wiley Subscription Services, Inc
• Subjects: Angiogenesis; Animals; Europium; Fluorescence; Hydroxides; In vitro testing; lanthanide nanoparticles; Lanthanides; Lanthanoid Series Elements - chemistry; Lanthanoid Series Elements - pharmacology; Nanoparticles; Nanoparticles - chemistry; Nanotechnology; Neovascularization, Physiologic - drug effects; reactive oxygen species; Reactive Oxygen Species - metabolism; Rods; Zebrafish; lanthanide nanoparticles; zebrafish; angiogenesis; reactive oxygen species
• ISSN: 1613-6810; 1613-6829
• DOI: 10.1002/smll.201600291

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, EuIII(OH)3 rods (Eu rods), EuIII(OH)3 spheres (Eu spheres), TbIII(OH)3 rods (Tb rods), and TbIII(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 H2O2 is a key factor in the process of proangiogenesis by lanthanide elemental nanoparticles. Nanoparticles with pro‐angiogenesis capability are identified by a high throughput in vitro cell based screen coupled with in vivo validation using vascular specific green fluorescent protein reporter transgenic zebrafish. Although the ionic forms of lanthanide elements for nanoparticle are capable of enhancing angiogenesis, nano‐structures is important for higher activity. The pro‐angiogenesis activity is mediated through production of reactive oxygen species.