Biocompatibility of ferritin-based nanoparticles as targeted MRI contrast agents

• Published in: Nanomedicine Vol. 12; no. 6; pp. 1735 - 1745
• Main Authors: Charlton, Jennifer R., MD, MSc, Pearl, Valeria M., BS, Denotti, Anna R., MD, Lee, Jonathan B., MD, Swaminathan, Sundararaman, MD, Scindia, Yogesh M., PhD, Charlton, Nathan P., MD, Baldelomar, Edwin J., BS, Beeman, Scott C., PhD, Bennett, Kevin M., PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2016
• Subjects: Animals; Cationic ferritin; Contrast Media; Ferritin; Ferritins; Horses; Internal Medicine; Iron; Kidney; Liver; Magnetic resonance imaging; Magnetic Resonance Imaging - methods; Male; Mice; Nanoparticles; Nephron number; Toxicity; MCV; urine protein/creatinine; Toxicity; high dose cationic ferritin; IHC; MRI; Ferritin; magnetic resonance image; UPC; HO-1; blood urea nitrogen; Kidney; BP; Cationic ferritin; GBM; maximum tolerated dose; 4-HNE; WBC; BUN; immunohistochemistry; hematoxylin and eosin; 4-hydroxynoneal; blood pressure; CF; white blood cell; H&E; heme oxygenase-1; Nephron number; Magnetic resonance imaging; native ferritin; mean corpuscular volume; NF; glomerular basement membrane; MTD; RO; HDCF; retro-orbital
• ISSN: 1549-9634; 1549-9642
• DOI: 10.1016/j.nano.2016.03.007

Abstract Ferritin is a naturally occurring iron storage protein, proposed as a clinically relevant nanoparticle with applications as a diagnostic and therapeutic agent. Cationic ferritin is a targeted, injectable contrast agent to measure kidney microstructure with MRI. Here, the toxicity of horse spleen ferritin is assessed as a step to clinical translation. Adult male mice received cationic, native and high dose cationic ferritin (CF, NF, or HDCF) or saline and were monitored for 3 weeks. Transient weight loss occurred in the ferritin groups with no difference in renal function parameters. Ferritin-injected mice demonstrated a lower serum iron 3 weeks after administration. In ferritin-injected animals pre-treated with hydrocortisone, there were no structural or weight differences in the kidneys, liver, lung, heart, or spleen. This study demonstrates a lack of significant detrimental effects of horse-derived ferritin-based nanoparticles at MRI-detectable doses, allowing further exploration of these agents in basic research and clinical diagnostics.