Nanoceria distribution and effects are mouse-strain dependent.

Area of Science:

• Nanomedicine and Toxicology
• Immunology
• Materials Science

Background:

• Nanoparticle clearance and biological interactions can differ between mouse strains with distinct immune profiles (Th1 vs. Th2).
• Understanding strain-dependent responses to engineered nanomaterials like nanoceria is crucial for safety and efficacy assessments.

Purpose of the Study:

• To investigate nanoceria (cerium oxide, CeO2 nanoparticle) uptake, distribution, and biological effects in C57BL/6 and BALB/c mice.
• To characterize cellular stress, oxidative damage, and bioprocessing of nanoceria as a function of mouse strain.

Main Methods:

• C57BL/6 and BALB/c mice were administered nanoceria via intraperitoneal injection.
• Organ tissues were analyzed for cerium content, cellular morphology (light and electron microscopy), and biomarkers of oxidative stress and inflammation (caspase-1, IL-1β, protein carbonyls).
• Elemental mapping and high-resolution microscopy were used to examine intracellular nanoceria bioprocessing.

Main Results:

• Nanoceria distribution varied by strain, with generally higher peripheral organ cerium in C57BL/6 mice.
• BALB/c mice exhibited greater liver caspase-1 elevation, suggesting inflammasome activation, and reduced liver vacuolation compared to C57BL/6 mice.
• Electron microscopy revealed rapid intracellular bioprocessing of nanoceria into cerium phosphate nanoneedles and strain-dependent ferritin accumulation patterns.

Conclusions:

• BALB/c mice demonstrated a more pronounced response to nanoceria, including inflammatory and cellular changes in the liver and spleen.
• Nanoceria undergoes rapid uptake and biotransformation into crystalline nanoneedles, with ferritin accumulation influenced by macrophage phenotype.
• Significant differences in nanoceria-induced effects between mouse strains highlight the importance of immune response in nanomaterial interactions.