Rare-earth orthovanadate nanoparticles trigger Ca²⁺-dependent eryptosis

Area of Science:

• Nanomedicine
• Toxicology
• Cell Biology

Background:

• Rare-earth orthovanadate nanoparticles (ReVO4:Eu3+) show promise in cancer photodynamic therapy.
• Their application is limited by potential toxicity.
• Eryptosis, or programmed red blood cell death, is a key concern for nanoparticle safety.

Purpose of the Study:

• To investigate the pro-eryptotic effects of GdVO4:Eu3+ and LaVO4:Eu3+ nanoparticles.
• To identify the mechanisms underlying nanoparticle-induced eryptosis.
• To evaluate their potential in managing eryptosis-related diseases.

Main Methods:

• Erythrocytes were incubated with varying concentrations of GdVO4:Eu3+ and LaVO4:Eu3+ nanoparticles.
• Flow cytometry was used to analyze cell membrane scrambling, shrinkage, reactive oxygen species (ROS) generation, and intracellular calcium levels.
• Confocal laser scanning microscopy assessed nanoparticle internalization.

Main Results:

• Both GdVO4:Eu3+ and LaVO4:Eu3+ nanoparticles induced eryptosis at 80 mg L−1.
• Eryptosis induction was mediated by elevated intracellular calcium, not ROS.
• LaVO4:Eu3+ nanoparticles showed a more significant increase in intracellular calcium compared to GdVO4:Eu3+.
• Small GdVO4:Eu3+ nanoparticles were internalized, while larger LaVO4:Eu3+ nanoparticles localized extracellularly.

Conclusions:

• GdVO4:Eu3+ and LaVO4:Eu3+ nanoparticles promote eryptosis in vitro via calcium signaling, independent of oxidative stress.
• Eryptosis serves as a valuable model for evaluating the nanotoxicity of these compounds.
• Understanding these mechanisms is crucial for developing safer nanomedicines.