T1-Enhanced MRI-visible nanoclusters for imaging-guided drug delivery.

Iron oxide nanoparticles with extremely low dimensions have recently been explored as positive (T1) contrast agent for magnetic resonance imaging (MRI). However, their small sizes lead to fast renal clearance and limit their use in elongated in vivo tracking or therapy monitoring. In this paper, we present a state of art approach to forming nanoclusters by crosslinking ultrasmall iron oxide nanoparticles with bovine serum albumin. This novel design not only maintains the T1 performance of the ultrasmall nanoparticles, but also significantly increases their blood circulation times from 15 minutes to over two hours. Our breast tumor model study also exhibited enhanced contrast at tumor sites for more than 24 hours. The ability of maintaining the T1 performance of the ultrasmall nanoparticles is significant, because previous studies have shown complete T1 loss or signal decrease upon polymer encapsulation. This design also shows great potential in encapsulating model drug molecules, which will greatly benefit the field of imaging-guided drug delivery.

Ketamine modulates hippocampal neurochemistry and functional connectivity: a combined magnetic resonance spectroscopy and resting-state fMRI study in healthy volunteers.

A growing body of evidence suggests glutamate excess in schizophrenia and that N-methyl-d-aspartate receptor (NMDAR) hypofunction on γ-aminobutyric acid (GABA) interneurons disinhibiting pyramidal cells may be relevant to this hyperglutamatergic state. To better understand how NMDAR hypofunction affects the brain, we used magnetic resonance spectroscopy and resting-state functional magnetic resonance imaging (MRI) to study the effects of ketamine on hippocampal neurometabolite levels and functional connectivity in 15 healthy human subjects. We observed a ketamine-induced increase in hippocampal Glx (glutamate+glutamine; F=3.76; P=0.04), a decrease in fronto-temporal (t=4.92, PFDR<0.05, kE=2198, x=-30, y=52, z=14) and temporo-parietal functional connectivity (t=5.07, PFDR<0.05, kE=6094, x=-28, y=-36, z=-2), and a possible link between connectivity changes and elevated Glx. Our data empirically support that hippocampal glutamatergic elevation and resting-state network alterations may arise from NMDAR hypofunction and establish a proof of principle whereby experimental modelling of a disorder can help mechanistically integrate distinct neuroimaging abnormalities in schizophrenia.

Shape-dependent cellular behaviors and relaxivity of iron oxide-based T1 MRI contrast agents.

Recent research efforts about iron oxide nanoparticles has focused on the development of iron oxide-based T1 contrast agents for magnetic resonance imaging (MRI), such as ultrasmall iron oxide nanospheres (USNPs <4 nm) and ultrathin nanowires (NW, diameter <4 nm). In this paper, we report the cellular uptake behaviors of these two types of ultrasmall scale nanostructures on HepG2 cells. Both these two nanostructures were functionalized with tannic acid and their physical and chemical properties were carefully analyzed before cellular tests. Both USNPs and NWs exhibited strong paramagnetic signals, a property suitable for T1 MRI contrast agents. The distinct shapes also caused much difference in their cellular uptake behaviors. Specifically, the uptake of USNPs was five times higher than that of NWs after 72 hours incubation. The shape-dependent cellular uptake can potentially lead to different blood circulation times, and subsequently different applications of these two types of ultrasmall nanostructures.