Lanthanide Hydroxide Nanoparticles Induce Angiogenesis via ROS-Sensitive Signaling

Area of Science:

• Biomaterials Science
• Nanotechnology
• Vascular Biology

Background:

• Europium hydroxide nanorods have shown potential in promoting angiogenesis.
• Further investigation is needed to explore other nanoparticles and their mechanisms for enhancing blood vessel formation.

Purpose of the Study:

• To identify novel nanoparticles that enhance angiogenesis.
• To elucidate the underlying molecular mechanisms of nanoparticle-induced proangiogenesis.

Main Methods:

• A high-throughput in vitro cell-based screening assay was utilized.
• In vivo validation was performed using vascular-specific green fluorescent protein reporter transgenic zebrafish.
• Screening identified europium (Eu) and terbium (Tb) based nanoparticles and their ionic forms.

Main Results:

• Europium hydroxide rods (Eu rods), europium hydroxide spheres (Eu spheres), terbium hydroxide rods (Tb rods), and terbium hydroxide spheres (Tb spheres) demonstrated significant proangiogenic activity.
• Ionic forms of europium nitrate (Eu) and terbium nitrate (Tb) also enhanced angiogenesis, but to a lesser extent than their nanoparticle counterparts.
• Nanoparticle synthesis further amplified the proangiogenic effect.

Conclusions:

• Lanthanide-based nanoparticles, particularly Eu and Tb hydroxides, are potent inducers of angiogenesis.
• The proangiogenic effect of these nanoparticles is significantly enhanced through synthesis into nanostructures.
• Reactive oxygen species, specifically hydrogen peroxide (H2O2), play a crucial role in lanthanide nanoparticle-mediated angiogenesis.