Hydrophilic packaging of iron oxide nanoclusters for highly sensitive imaging

Abstract

Superparamagnetic iron oxide nanoparticles (SPIONs) are used as imaging probes to provide contrast in magnetic resonance images. Successful use of SPIONs in targeted applications greatly depends on their ability to generate contrast, even at low levels of accumulation, in the tissue of interest. In the present study, we report that SPION nanoclusters packaged to a controlled size by a hyperbranched polyglycerol (HPG) can target tissue defects and have a high relaxivity of 719 mM−1s−1, which was close to their theoretical maximal limit. The resulting nanoclusters were able to identify regions of defective vasculature in an ischemic murine hindlimb using MRI with iron doses that were 5–10 fold lower than those typically used in preclinical studies. Such high relaxivity was attributed to the molecular architecture of HPG, which mimics that of the water retentive polysaccharide, glycogen. The results of this study will be broadly useful in sensitive imaging applications.

Preparation and Application of Iron Oxide Nanoclusters

“…The biomedical applications of iron oxide nanoclusters have been focused on magnetically triggered drug release [48][49][50][51] and MRI contrast agents with high sensitivity [30,[52][53][54]. For magnetically triggered drug release, either iron oxide nanoparticles (>10 nm) and drugs were colocalized in nanocarriers [55] or porous iron oxide nanoclusters were created to increase drug loading by surface adsorption [16].…”

“…Because of their larger sizes, these capsules were sensitive to ultrasound, which enhanced drug localization at the tumor site with ultrasound treatment (Figure 9d). T2 MRI contrast agents are mainly superparamagnetic nanoparticles, and nanocluster formation increases the magnetic signal and subsequently enhances the imaging sensitivity or cell labeling efficiency [24,30,52,53,56,[65][66][67]. For example, differently sized iron oxide nanoclusters via solvothermal synthesis showed higher r2 relaxivity for nanocluster sizes of around 50-60 nm.…”

Redoxable heteronanocrystals functioning magnetic relaxation switch for activatable T1 and T2 dual-mode magnetic resonance imaging

“…Alternatively, T 2 contrast agents commonly consist of superparamagnetic nanoparticles, such as superparamagnetic iron oxide nanoparticles (SPION), and can be magnetically saturated by the typical magnetic field strengths in MRI scanners [2,10]. These agents work by shortening the traverse relaxation time (T 2 ) of water protons in their vicinity [11,12].…”

“…Magnetic resonance (MR) imaging has been widely applied in a variety of clinical diagnostic fields as a powerful noninvasive technique [1,2]. MR imaging is particularly appealing because it can provide anatomical images of tissues and organs with excellent spatial resolution [3,4].…”

Zwitterionic poly(amido amine) based nanogels

“…254 Encapsulation of SPIONs into nanogels has been reported on a few ocasions. 86, [255][256][257][258] Zhang et al showed the encapsulation of SPIONs in bioreducible zwitterionic nanogels, which remained stable under physiological conditions and quickly released encapsulated SPIONs and drugs after exposure to dithiothreitol (DTT). 86 Recently, Liu et al prepared theranostic nanogels, crosslinked by boronate-coated SPIONs and a poly(vinyl alcohol)-pVCl copolymer, which exhibited drug release upon exposure to glucose.…”