Sensitive T2 MRI Contrast Agents from the Rational Design of Iron Oxide Nanoparticle Surface Coatings

Abstract

Iron oxide nanoparticles are an FDA-approved and gadolinium-free alternative to conventional magnetic resonance imaging (MRI) contrast agents. While their magnetic cores are responsible for T 2 contrast, the nonmagnetic polymers at the particle interfaces can affect the diffusion of bulk water near the particles. We show here how this interaction can alter the relaxation dynamics of water protons and, consequently, the nanoparticle's contrast performance. Libraries of iron oxide nanocrystals of different core diameters and surface coatings can form biocompatible, non-cytotoxic, and colloidally stable suspensions with excellent MRI properties. Both the grafting density and thickness of polymer coatings influence the amount of time water protons spend around a nanoparticle and thus their contrast agent performance. Characterization of the diameter-dependent contrast performance of these materials revealed that nanoparticles with dense, hydrophilic polymer coatings reached the static dephasing regime, and optimal T 2 relaxivity, at smaller dimensions than other systems. We rationalized that such coatings offered a slow compartment for water diffusion near the magnetic particle, resulting in an effective diffusion constant lower than bulk water. By manipulating the surface coating and core diameter together, we could generate a material with one of the largest T 2 relaxivities ever reported (510 mM −1 s −1 ) for an isolated nanocrystal. This conceptual framework can explain the complex structure−performance trends of this class of T 2 contrast agents and those already reported in the existing literature. Water diffusion at iron oxide nanocrystals (IONCs) interfaces is an essential consideration in designing sensitive and possibly responsive T 2 MRI contrast agents.

Unveiling the Biologically Dynamic Degradation of Iron Oxide Nanoparticles via a Continuous Flow System

“…Additionally, the slight increase in r 2 can be explained by the adsorption of proteins, which slows the diffusion of water protons around nanoparticles. [ 45 ] On the other hand, the decrease in r 1 and increase in r 2 of nanoparticles in the GSH solution can be attributed to the aggregation of particles, [ 46 ] as supported by the DLS results shown in Figure 3f. The aggregation of nanoparticles induces changes in the local magnetic field, leading to altered relaxation properties and subsequently affecting the measured relaxivities and T 1‐ and T 2‐weighted images (Figure 4c,d).…”

PEG-Coated MnZn Ferrite Nanoparticles with Hierarchical Structure as MRI Contrast Agent

“…However, it must be noted that not only some parameters of ferrite nanoparticles such as the crystallinity, composition, size, morphology, and magnetic properties are responsible for T 2 contrast but also the characteristics of nonmagnetic polymers as coatings must be considered. Cho et al [ 32 ] have recently reported that higher T 2 relaxivity could be achieved by manipulating the features of surface coating and ferrite nanoparticles together.…”

Advances in the application of manganese dioxide and its composites for theranostics

“…Specifically, pores on the nanoparticles could restrict the diffusion of water molecules, which would lead to increased interactions between water protons and the MnO 2 nanoparticles and thus further enhance the T 2 relaxation. 83…”

“…Specifically, pores on the nanoparticles could restrict the diffusion of water molecules, which would lead to increased interactions between water protons and the MnO 2 nanoparticles and thus further enhance the T 2 relaxation. 83 K. Deka et al 84 investigated manganese oxide nanoparticles infused in mesoporous three-dimensional carbon frames as MRI contrast agents. Their research revealed a remarkable increase in T 2 contrast by controlling the interaction between magnetic ions and water (Fig.…”