ABSTRACT

Iron oxide nanoparticles (IONPs) have found many applications in biomedicine, particularly as biocompatible contrast agents for magnetic resonance imaging (MRI). IONPs are used in the detection of hepatic tumours, for the staging of cancer based on contrast effects in the lymph nodes, and as vascular contrast agents. However, a major challenge toward effective applications is to preserve the colloidal stability of these products in the blood and other biological fluids (e.g. lymph and urine). Without an adequate layer of stabilizing molecules on their surfaces, IONPs usually agglomerate instantly in aqueous conditions. Coating the surface of IONPs with biocompatible polymers such as polyethylene glycol (PEG) and related derivatives is essential to the development of more stable colloids. However, grafting linear polymer chains at the surface of IONPs through a single functional anchoring site often leads to colloidal instability and, thus, gradual agglomeration. To increase the strength of grafting, to minimize the risk of chain detachment due to the breakage of one single bond and to ultimately improve colloidal stability, new functional polymeric constructs have been developed featuring several functional groups per chain. This chapter begins with a review of the main physical parameters of ultrasmall IONPs required to achieve efficient and functional MRI contrast agents. Then, we introduce the concept of multidentate block copolymers for IONP coatings, followed by a description of the size, physicochemical, magnetic and relaxometric characteristics of the resulting new colloids. This new strategy for coating IONPs provides enhanced binding strength and high colloidal stability while enabling the synthesis of ultrasmall nanoparticles with strong ‘positive’ contrast enhancement potential.