Physical characterization of iron oxide nanoparticles in magnetoferritin

L. Melnikova¹ - Z. Mitroova¹ - M. Timko¹ - J. Kovaċ¹ - M. Koralewski² - M. Pochylski² - M. V. Avdeev³ - V. I. Petrenko^{3, 4} - V. M. Garamus⁵ - L. Almasy⁶ - P. Kopċanský¹

¹ Institute of Experimental Physics, SAS, Watsonova 47, 040 01 Košice, Slovakia e-Mail: melnikova@saske.sk
² Faculty of Physics, Adam Mickiewicz University, Umultowska 85, 61-614 Pozna\'{n Poland
³ Frank Laboratory of Neutron Physics, Joint Institute for Nuclear Research, Dubna, Russia
⁴ Taras Shevchenko National University of Kyiv, Kyiv, Ukraine
⁵ Helmholtz-Zentrum Geesthacht, Zentrum für Material- und Küstenforschung, Geesthacht, Germany
⁶ Wigner Research Centre for Physics, HAS, H-1525, Budapest, P.O. Box 49, Hungary

Abstract
Natural ferritin is the iron-storage protein of animals, plants, and bacteria. It is a spherical biomacromolecule of external diameter about 12 nm composed of 24 protein subunits arranged as a hollow sphere of approximately 8 nm in diameter. Inside the sphere, iron is stored in the ferric oxidation state as a complex molecule with a crystallographic structure similar to mineral ferrihydrite. By a proper chemical process, it is possible to use the empty protein shell of ferritin, i.e. apoferritin, as a confined environment, in which magnetic iron oxide nanoparticles can be synthesized forming a biocompatible ferrofluid called magnetoferritin [1]. The latest studies show that brain ferritin [2] in patients with the Alzheimer's disease [3] has a polyphase structure, incorporating also magnetite. The structure, quality and quantity of the iron core composition in the brain ferritin have not been fully determined yet, and it has not been established whether they are related to the origin of neurodegenerative diseases or to their consequences [4, 5]. For these reasons, by combining different techniques it is necessary to fully characterize the structure and the physico-chemical properties of ferritin and distinguish between magnetic structures, especially for understanding the role of magnetite presence in the development of neurodegenerative diseases. Of particular interest is the search for methods allowing detection of magnetite inside ferritin proteins in vivo and inside magnetoferritin as a model system in vitro, respectively. Magnetoferritin is a relatively new biocompatible nanomaterial with continuously increasing popularity in many fields of science from medicine through nanotechnology up to physics. If compared with physiological ferritin, magnetoferritin contains magnetic nanoparticles (Fe ₃O ₄, γ-Fe ₂O ₃) surrounded by the empty protein shell (apoferritin). The problem of toxicity and side effects of magnetic nanoparticles in organs and tissues is minimized due to the protein nature of this unique material, which is important for many possible applications in clinical practice as a drug carrier, contrast medium in radiodiagnostics, or in magnetic hyperthermia therapy. In addition to biocompatibility, another advantage of magnetoferritin for biotechnological applications is a relatively short time of controlled synthesis adapted to the formation of magnetite specifically inside the protein cavity and creation the magnetoferritin molecule. Figs 3, Refs 6.