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1. Quantitative analysis of zero-field splitting parameter distributions in Gd( iii ) complexes

   https://doi.org/10.1039/c7cp08507a  

   Clayton, Jessica A.; Keller, Katharina; Qi, Mian; Wegner, Julia; Koch, Vanessa; Hintz, Henrik; Godt, Adelheid; Han, Songi; Jeschke, Gunnar; Sherwin, Mark S.; et al (January 2018, Physical Chemistry Chemical Physics)

   The magnetic properties of paramagnetic species with spin S > 1/2 are parameterized by the familiar g tensor as well as “zero-field splitting” (ZFS) terms that break the degeneracy between spin states even in the absence of a magnetic field. In this work, we determine the mean values and distributions of the ZFS parameters D and E for six Gd( iii ) complexes ( S = 7/2) and critically discuss the accuracy of such determination. EPR spectra of the Gd( iii ) complexes were recorded in glassy frozen solutions at 10 K or below at Q-band (∼34 GHz), W-band (∼94 GHz) and G-band (240 GHz) frequencies, and simulated with two widely used models for the form of the distributions of the ZFS parameters D and E . We find that the form of the distribution of the ZFS parameter D is bimodal, consisting roughly of two Gaussians centered at D and − D with unequal amplitudes. The extracted values of D ( σ D ) for the six complexes are, in MHz: Gd-NO 3 Pic, 485 ± 20 (155 ± 37); Gd-DOTA/Gd-maleimide-DOTA, −714 ± 43 (328 ± 99); iodo-(Gd-PyMTA)/MOMethynyl-(Gd-PyMTA), 1213 ± 60 (418 ± 141); Gd-TAHA, 1361 ± 69 (457 ± 178); iodo-Gd-PCTA-[12], 1861 ± 135 (467 ± 292); and Gd-PyDTTA, 1830 ± 105 (390 ± 242). The sign of D was adjusted based on the Gaussian component with larger amplitude. We relate the extracted P ( D ) distributions to the structure of the individual Gd( iii ) complexes by fitting them to a model that superposes the contribution to the D tensor from each coordinating atom of the ligand. Using this model, we predict D , σ D , and E values for several additional Gd( iii ) complexes that were not measured in this work. The results of this paper may be useful as benchmarks for the verification of quantum chemical calculations of ZFS parameters, and point the way to designing Gd( iii ) complexes for particular applications and estimating their magnetic properties a priori . 

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2. Iron oxide nanoparticles as positive T1 contrast agents for low-field magnetic resonance imaging at 64 mT

   https://doi.org/10.1038/s41598-023-38222-6  

   Oberdick, Samuel D.; Jordanova, Kalina V.; Lundstrom, John T.; Parigi, Giacomo; Poorman, Megan E.; Zabow, Gary; Keenan, Kathryn E. (December 2023, Scientific Reports)

   We have investigated the efficacy of superparamagnetic iron oxide nanoparticles (SPIONs) as positive T1 contrast agents for low-field magnetic resonance imaging (MRI) at 64 millitesla (mT). Iron oxide-based agents, such as the FDA-approved ferumoxytol, were measured using a variety of techniques to evaluate T1 contrast at 64 mT. Additionally, we characterized monodispersed carboxylic acid-coated SPIONs with a range of diameters (4.9–15.7 nm) in order to understand size-dependent properties of T1 contrast at low-field. MRI contrast properties were measured using 64 mT MRI, magnetometry, and nuclear magnetic resonance dispersion (NMRD). We also measured MRI contrast at 3 T to provide comparison to a standard clinical field strength. SPIONs have the capacity to perform well as T1 contrast agents at 64 mT, with measured longitudinal relaxivity (r1) values of up to 67 L mmol−1 s−1, more than an order of magnitude higher than corresponding r1 values at 3 T. The particles exhibit size-dependent longitudinal relaxivities and outperform a commercial Gd-based agent (gadobenate dimeglumine) by more than eight-fold at physiological temperatures. Additionally, we characterize the ratio of transverse to longitudinal relaxivity, r2/r1 and find that it is ~ 1 for the SPION based agents at 64 mT, indicating a favorable balance of relaxivities for T1-weighted contrast imaging. We also correlate the magnetic and structural properties of the particles with models of nanoparticle relaxivity to understand generation of T1 contrast. These experiments show that SPIONs, at low fields being targeted for point-of-care low-field MRI systems, have a unique combination of magnetic and structural properties that produce large T1 relaxivities. 

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3. Formation of Microcages from a Collagen Mimetic Peptide via Metal-Ligand Interactions

   https://doi.org/10.3390/molecules26164888  

   Gleaton, Jeremy; Curtis, Ryan W.; Chmielewski, Jean (August 2021, Molecules)

   Here, the hierarchical assembly of a collagen mimetic peptide (CMP) displaying four bipyridine moieties is described. The CMP was capable of forming triple helices followed by self-assembly into disks and domes. Treatment of these disks and domes with metal ions such as Fe(II), Cu(II), Zn(II), Co(II), and Ru(III) triggered the formation of microcages, and micron-sized cup-like structures. Mechanistic studies suggest that the formation of the microcages proceeds from the disks and domes in a metal-dependent fashion. Fluorescently-labeled dextrans were encapsulated within the cages and displayed a time-dependent release using thermal conditions. 

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4. Human Forebrain Organoid-Derived Extracellular Vesicle Labeling with Iron Oxides for In Vitro Magnetic Resonance Imaging

   https://doi.org/10.3390/biomedicines10123060  

   Liu, Chang; Helsper, Shannon; Marzano, Mark; Chen, Xingchi; Muok, Laureana; Esmonde, Colin; Zeng, Changchun; Sun, Li; Grant, Samuel C.; Li, Yan (December 2022, Biomedicines)

   The significant roles of extracellular vesicles (EVs) as intracellular mediators, disease biomarkers, and therapeutic agents, make them a scientific hotspot. In particular, EVs secreted by human stem cells show significance in treating neurological disorders, such as Alzheimer’s disease and ischemic stroke. However, the clinical applications of EVs are limited due to their poor targeting capabilities and low therapeutic efficacies after intravenous administration. Superparamagnetic iron oxide (SPIO) nanoparticles are biocompatible and have been shown to improve the targeting ability of EVs. In particular, ultrasmall SPIO (USPIO, <50 nm) are more suitable for labeling nanoscale EVs due to their small size. In this study, induced forebrain neural progenitor cortical organoids (iNPCo) were differentiated from human induced pluripotent stem cells (iPSCs), and the iNPCo expressed FOXG1, Nkx2.1, α-catenin, as well as β-tubulin III. EVs were isolated from iNPCo media, then loaded with USPIOs by sonication. Size and concentration of EV particles were measured by nanoparticle tracking analysis, and no significant changes were observed in size distribution before and after sonication, but the concentration decreased after labeling. miR-21 and miR-133b decreased after sonication. Magnetic resonance imaging (MRI) demonstrated contrast visualized for the USPIO labeled EVs embedded in agarose gel phantoms. Upon calculation, USPIO labeled EVs exhibited considerably shorter relaxation times, quantified as T2 and T2* values, reducing the signal intensity and generating higher MRI contrast compared to unlabeled EVs and gel only. Our study demonstrated that USPIO labeling was a feasible approach for in vitro tracking of brain organoid-derived EVs, which paves the way for further in vivo examination. 

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5. Real‐Time, In Situ Imaging of Macrophages via Phase‐Change Peptide Nanoemulsions

   https://doi.org/10.1002/smll.202301673  

   Kim, Inhye; Elliott, Jacob C.; Lawanprasert, Atip; Wood, Grace M.; Simon, Julianna C.; Medina, Scott H. (November 2023, Small)

   Macrophages are specialized phagocytes that play central roles in immunity and tissue repair. Their diverse functionalities have led to an evolution of new allogenic and autologous macrophage products. However, realizing the full therapeutic potential of these cell‐based therapies requires development of imaging technologies that can track immune cell migration within tissues in real‐time. Such innovations will not only inform treatment regimens and empower interpretation of therapeutic outcomes but also enable prediction and early intervention during adverse events. Here, phase‐changing nanoemulsion contrast agents are reported that permit real‐time, continuous, and high‐fidelity ultrasound imaging of macrophages in situ. Using a de novo designed peptide emulsifier, liquid perfluorocarbon nanoemulsions are prepared and show that rational control over interfacial peptide assembly affords formulations with tunable acoustic sensitivity, macrophage internalization, and in cellulo stability. Imaging experiments demonstrate that emulsion‐loaded macrophages can be readily visualized using standard diagnostic B‐mode and Doppler ultrasound modalities. This allows on‐demand and long‐term tracking of macrophages within porcine coronary arteries, as an exemplary model. The results demonstrate that this platform is poised to open new opportunities for non‐invasive, contrast‐enhanced imaging of cell‐based immunotherapies in tissues, while leveraging the low‐cost, portable, and safe nature of diagnostic ultrasound. 

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