title: Toxicity and Biodistribution of Activated and Non-activated Intravenous Iron Oxide Nanoparticles.
abstract: The use of nanoparticles in medical treatment has prompted the question of their safety. In this study, the pathophysiology and biodistribution of three different concentrations of intravenously-delivered dextran-coated Fe3O4 iron oxide nanoparticles (IONP) were evaluated in mice. Some groups of mice were exposed to an AC magnetic field (AMF) at levels comparable with those proposed for cancer treatments. Iron biodistribution analysis for both AMF and non-AMF treated mice was performed for all three concentrations used (.6 mg Fe/mouse, 1.8 mg Fe/mouse, and 5.6 mg Fe/mouse). Blood urea nitrogen, alanine transaminase, alkaline phosphatase, total serum protein, and creatinine were also assessed at 4 hours, 7 days, and 14 days post-injection. Histological analysis of lung, spleen, heart, liver, and kidney tissue was conducted at 7 and 14 days post-injection. Prussian blue and H&E stains were used to histomorphometrically assess iron content in the tissues studied. Preliminary results demonstrate small temporary elevation in liver enzymes and hepatocyte vacuolization at all iron concentrations studied. Liver and spleen were the primary sites of IONP deposition. None of the animals demonstrated systemic or local toxicity or illness, with or without AMF activation.
authors.affiliation: Thayer School of Engineering, Dartmouth College, Hanover, NH 03755 USA.
authors.forename: Ja
authors.initials: J
authors.lastname: Tate
authors.affiliation: Thayer School of Engineering, Dartmouth College, Hanover, NH 03755 USA.
authors.forename: Ja
authors.initials: J
authors.lastname: Ogden
authors.affiliation: Dartmouth Medical School, Hanover, NH 03755 USA.
authors.forename: Rr
authors.initials: R
authors.lastname: Strawbridge
authors.affiliation: Thayer School of Engineering, Dartmouth College, Hanover, NH 03755 USA.
authors.forename: Ze
authors.initials: Z
authors.lastname: Pierce
authors.affiliation: Dartmouth Medical School, Hanover, NH 03755 USA ; Thayer School of Engineering, Dartmouth College, Hanover, NH 03755 USA.
authors.forename: Pj
authors.initials: P
authors.lastname: Hoopes
keywords: Iron oxide; alternating magnetic field; biodistribution; hyperthermia; mouse; nanoparticle; toxicity