Doping engineering of iron oxide nanoparticles towards high performance and biocompatible <i>T</i> <sub>1</sub> ‐weighted MRI contrast agents
Xue Xu, Pingli Dong, Yuyun Chai, Yang Run, Zhenhui Ma, Chichong Lu
Abstract
Abstract Extremely small‐sized iron oxide nanoparticles (IONPs) are of great interest in magnetic resonance imaging (MRI) due to their biosafety as an alternative to clinical gadolinium (III) complexes‐based contrast agents. Especially when the particle size is less than 10 nm, it has strong diffusion ability and deep penetration distance in tumor tissue. Substitution doping can significantly enhance the T 1 contrast effect of nanoparticles by regulating the surface exposed atoms. However, the nucleation and growth processes of multi‐component synthesis systems are complex and difficult to be accurately controlled, leading to great challenges in the synthesis of ultra‐small‐sized nanoparticles with different components and sizes. Here, extremely small‐sized superparamagnetic gadolinium‐doped iron oxide nanoparticles (GdIONPs, Gd x Fe 3− x O 4 NPs) with adjustable doping amount and controllable size in the range of 3.5–7.5 nm were synthesized by thermal decomposition. Then, as‐synthesized GdIONPs were surface modified with a highly water‐soluble and biocompatible carboxyl–polyethylene glycol–phosphoric acid ligand with high binding affinity. Gd 0.65 Fe 2.35 O 4 NPs exhibited very high r 1 relaxivity of 10.6 mmol –1 ·L·s –1 in terms of all metal concentrations and 49.0 mmol –1 ·L·s –1 in terms of gadolinium alone, respectively, 3 and 14 times higher than clinical T 1 contrast agents (Gd‐DTPA). GdIONPs can continuously obtain high resolution images of blood vessels, and can be used as an efficient and multifunctional contrast agent for MR T 1 imaging. This stable and efficient doping strategy provides an easy and effective method to individually optimize the magnetic properties of complex oxides and their relaxation effects for a variety of biomedical applications.