ABSTRACT
In this regard, a significant effort of many radiology research groups has been dedicated to the task of designing biocompatible, ultrasmall, nano-size particles and macromolecules ranging from 10 to 50 nm in diameter that can be utilized as contrast agents for MRI. The push for designing such small particles was traditionally based on the assumption that nanoparticles, which have hydrodynamic radii below 100 nm, should have a substantially better chance of crossing vascular and tissue barriers and should penetrate the interstitium better than larger particles of several hundred nanometers in diameter. A smaller size of the particles was thought to have a potential of eventually translating into more even distribution in the tissue. High-resolution electron and atomic force microscopies combined with the more advanced techniques of sample preparation resulted in more detailed information about the ultrastructure and morphology of the nanoparticles. The developed nanoparticles, both paramagnetic and superparamagnetic, have several common features. They usually have inner cores containing a plurality of atoms of paramagnetic or superparamagnetic metals, and these cores are coated with a surface layer or layers of stabilizing molecules. The surface coating is amenable to covalent or noncovalent linking to the cores either during the synthesis, or after “naked” nanoparticle fractionation, and is designed to stabilize the core nanoparticles with the formation of stable colloidal solutions. This renders the particles hydrophilic, biocompatible, and potentially less susceptible to the adsorption of proteins. The latter, in turn, is believed to make nanoparticles less detectable for surveying and resident tissue macrophages and other cells of the reticulo-endothelial system (RES). Many of the developed nanoparticle types were at some point regarded as potential platforms for designing targeted contrast agents. The latter is frequently associated with certain limitations in terms of design and chemical composition. The common types of nanoparticle-size MR contrast agents as well as recent innovations and their applications are described below.
