title: Biocompatibility of ferritin-based nanoparticles as targeted MRI contrast agents.
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 3weeks. Transient weight loss occurred in the ferritin groups with no difference in renal function parameters. Ferritin-injected mice demonstrated a lower serum iron 3weeks 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.
authors.affiliation: University of Virginia, Department of Pediatrics, Division of Nephrology, Charlottesville VA, USA. Electronic address: jrc6n@virginia.edu.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Charlton
authors.affiliation: University of Virginia, Department of Pediatrics, Division of Nephrology, Charlottesville VA, USA. Electronic address: vmb3f@virginia.edu.
authors.forename: Valeria M
authors.initials: VM
authors.lastname: Pearl
authors.affiliation: Ospedale Regionale per le Microcitemie, University of Cagliari, Italy, Department of Pediatrics. Electronic address: an.den@hotmail.it.
authors.forename: Anna R
authors.initials: AR
authors.lastname: Denotti
authors.affiliation: Eastern Virginia Medical School, Department of Pediatrics, Norfolk, VA, USA. Electronic address: jbl5c@virginia.edu.
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Lee
authors.affiliation: University of Virginia, Center for Immunity, Inflammation and Regenerative Medicine and Department of Medicine, Division of Nephrology, Charlottesville VA, USA. Electronic address: ss4sa@virginia.edu.
authors.forename: Sundararaman
authors.initials: S
authors.lastname: Swaminathan
authors.affiliation: University of Virginia, Center for Immunity, Inflammation and Regenerative Medicine and Department of Medicine, Division of Nephrology, Charlottesville VA, USA. Electronic address: ys9t@virginia.edu.
authors.forename: Yogesh M
authors.initials: YM
authors.lastname: Scindia
authors.affiliation: University of Virginia, Department of Emergency Medicine, Division of Medical Toxicology, Charlottesville, VA, USA. Electronic address: npc8a@virginia.edu.
authors.forename: Nathan P
authors.initials: NP
authors.lastname: Charlton
authors.affiliation: University of Hawaii at Manoa, Department of Physics, Honolulu, HI, USA. Electronic address: ebaldelo@hawaii.edu.
authors.forename: Edwin J
authors.initials: EJ
authors.lastname: Baldelomar
authors.affiliation: Washington University School of Medicine, Department of Radiology, St. Louis, MO, USA. Electronic address: beemans@mir.wustl.edu.
authors.forename: Scott C
authors.initials: SC
authors.lastname: Beeman
authors.affiliation: University of Hawaii at Manoa, Department of Biology, Honolulu, HI. Electronic address: kevinben@hawaii.edu.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Bennett
mesh_terms: D000818:Animals; D003287:Contrast Media; D005293:Ferritins; D006736:Horses; D007501:Iron; D008099:Liver; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D053758:Nanoparticles
chemical_list: D003287:Contrast Media; D005293:Ferritins; D007501:Iron
keywords: Cationic ferritin; Ferritin; Kidney; Magnetic resonance imaging; Nephron number; Toxicity