Superparamagnetic Iron Oxide Nanoparticles-Current and Prospective Medical Applications

Abstract

The recent, fast development of nanotechnology is reflected in the medical sciences. Superparamagnetic Iron Oxide Nanoparticles (SPIONs) are an excellent example. Thanks to their superparamagnetic properties, SPIONs have found application in Magnetic Resonance Imaging (MRI) and magnetic hyperthermia. Unlike bulk iron, SPIONs do not have remnant magnetization in the absence of the external magnetic field; therefore, a precise remote control over their action is possible. This makes them also useful as a component of the advanced drug delivery systems. Due to their easy synthesis, biocompatibility, multifunctionality, and possibility of further surface modification with various chemical agents, SPIONs could support many fields of medicine. SPIONs have also some disadvantages, such as their high uptake by macrophages. Nevertheless, based on the ongoing studies, they seem to be very promising in oncological therapy (especially in the brain, breast, prostate, and pancreatic tumors). The main goal of our paper is, therefore, to present the basic properties of SPIONs, to discuss their current role in medicine, and to review their applications in order to inspire future developments of new, improved SPION systems.

Keywords: MRI; SPION; antibodies; hyperthermia; iron oxide; toxicity.

Figure 1

A schematic presentation of a SPION (Superparamagnetic Iron Oxide Nanoparticle): The core radius ranges from 5 to 15 nm, and the hydrodynamic radius (core with shell and water coat) is between 20–150 nm. Unless there is a magnetic field, magnetization equals 0. As shown, SPIONs could be easily coupled with antibodies that facilitates the majority of the SPION applications discovered so far.

Figure 2

The substances most frequently used as a coating for SPIONs: (1) PEG (Poly(Ethylene Glycol)), (2) PVA (Poly(Vinyl Alcohol)), (3) PVP (Poly(Vinyl Pyrrolidine)), (4) chitosan, and (5) dextran. The figure also sums up the most important parameters that are affected by coating.

Figure 3

A schematic representation of the antigenic peptide delivery by Hsp70–SPIONs into the dendritic cells (reprinted from Reference [29] with permission from Elsevier).

Figure 4

The scheme presenting the main idea of MRI. Upper part: The variable B₁ field in the form of a radiofrequency (RF) pulse rotates the magnetization to the transverse plane. Lower part: After the RF pulse is switched off, the system relaxes in time until equilibrium is reached, generating a FID signal. The processes leading to thermal equilibrium after RF pulse can be described as longitudinal (spin-lattice) relaxation, with characteristic constant T₁, and transverse (spin-spin) relaxation characterized by T₂. The first process occurs due to the dissipation of the absorbed energy to the surrounding environment, while the second results from the energy redistribution among the nuclei. The MRI contrasts improve the quality of the MRI image via influencing T₁ or T₂ of the surrounding tissue. Water protons in different tissues have different T₁ and T₂, a phenomenon that provides MRI contrast. T₁ is shortened by the interactions of the observed nuclei with paramagnetic agents and by a limited mobility of H₂O molecules (observed in more viscous tissues). T₂ is also shortened by lower molecular mobility. SPIONs are mainly negative T₂ contrast agents. When accumulated in the tissue, they shorten T₂, decreasing signal intensity, and provide a negative contrast enhancement. It is also suggested that if SPIONs’ particles are small enough (<10 nm), they could act as T₁ positive contrast agents [40].

Figure 5

(a) The synthesis and surface coating of SPIONs and FA-SPIONs; (b) The DOX-loaded FA-SPIONs (DOX- anticancer drug, doxorubicin) for FA-mediated and magnetically-targeted drug delivery to the tumor and the MR imaging (reprinted from Reference [73] with permission from Elsevier).