Rapid microwave-assisted synthesis of dextran-coated iron oxide nanoparticles for magnetic resonance imaging.

Currently, magnetic iron oxide nanoparticles are the only nanosized magnetic resonance imaging (MRI) contrast agents approved for clinical use, yet commercial manufacturing of these agents has been limited or discontinued. Though there is still widespread demand for these particles both for clinical use and research, they are difficult to obtain commercially, and complicated syntheses make in-house preparation unfeasible for most biological research labs or clinics. To make commercial production viable and increase accessibility of these products, it is crucial to develop simple, rapid and reproducible preparations of biocompatible iron oxide nanoparticles. Here, we report a rapid, straightforward microwave-assisted synthesis of superparamagnetic dextran-coated iron oxide nanoparticles. The nanoparticles were produced in two hydrodynamic sizes with differing core morphologies by varying the synthetic method as either a two-step or single-step process. A striking benefit of these methods is the ability to obtain swift and consistent results without the necessity for air-, pH- or temperature-sensitive techniques; therefore, reaction times and complex manufacturing processes are greatly reduced as compared to conventional synthetic methods. This is a great benefit for cost-effective translation to commercial production. The nanoparticles are found to be superparamagnetic and exhibit properties consistent for use in MRI. In addition, the dextran coating imparts the water solubility and biocompatibility necessary for in vivo utilization.

Modulation of T2 relaxation time by light-induced, reversible aggregation of magnetic nanoparticles.

A reversible T2 contrast agent consisting of cross-linked anionic dextran coated iron oxide nanoparticles covalently coupled to a light-sensitive spiropyran (SP)/merocyanine (MC) motif was synthesized and characterized. In aqueous solution, light induced isomerization of the molecular switches between the hydrophobic SP isomer and hydrophilic MC isomer directs the aggregation and dispersion of the nanoparticles, respectively. When in the dark, where the MC form dominates, the probe has a T2 relaxation time of 37.09 ms (60 MHz, 37 degrees C) and two size populations at 70 and 540 nm. After irradiation with visible light, the T2 relaxation time is shortened 33.7%, and the size correspondingly shifts to a single population at 520 nm upon aggregation. This "smart" T2 agent provides the advantage of reversibility which may enable dynamic monitoring with MRI. In addition, the light responsiveness of this agent suggests the potential to employ them as MRI gene reporters for the luciferase expression system.

Synthesis and characterization of a redox- and light-sensitive MRI contrast agent.

A redox- and light-sensitive, T(1)-weighted magnetic resonance imaging (MRI) contrast agent which tethers a spiropyran(SP)/merocyanine(MC) motif to a Gd-DO3A moiety was synthesized and characterized. When in the dark, the probe is in its MC form which has an r(1) relaxivity of 2.51 mM(-1)s(-1) (60MHz, 37°C). After irradiation with visible light or mixing with NADH, the probe experiences an isomerization and the r(1) relaxivity decreased 18% and 26%, respectively. Additionally, the signal intensity in MRI showed an observable decrease after the compound was mixed with NADH.

Activatable T1 and T2 magnetic resonance imaging contrast agents.

Magnetic resonance imaging (MRI) has become one of the most important diagnosis tools available in medicine. Typically MRI is not capable of sensing biochemical activities. However, recently emerged activatable MRI contrast agents (CAs), whose relaxivity is variable in response to a specific parameter change in the surrounding physiological microenvironment, potentially allow for MRI to indicate biological processes. Among the various factors influencing the relaxivity of a CA, the number of inner-sphere water molecules (q) directly coordinated to the metal center, the residence time of the coordinated water molecule (τ (m)), and the rotational correlation time representing the molecular tumbling time of a complex (τ (R)) contribute strongly to the relaxivity of an activatable CA. Tuning the ligand structure and properties has been the subject of intensive research for activatable MR CA designs. This review summarizes a variety of activatable MRI CAs sensitive to common variables in microenvironment in vivo, i.e., pH, luminescence, metal ions, redox, and enzymes, etc., with emphasis on the influence of ligand design on parameters q, τ (m), and τ (R).