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1. 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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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. ( July 2023 , Scientific Reports)

   We have investigated the efficacy of superparamagnetic iron oxide nanoparticles (SPIONs) as positive T₁contrast 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 T₁contrast 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 T₁contrast 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 T₁contrast 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 r₁values 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/r₁and 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 T₁contrast. 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 T₁relaxivities.

    

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3. The onset of rare earth metallosis begins with renal gadolinium-rich nanoparticles from magnetic resonance imaging contrast agent exposure

   https://doi.org/10.1038/s41598-023-28666-1  

   DeAguero, Joshua ; Howard, Tamara ; Kusewitt, Donna ; Brearley, Adrian ; Ali, Abdul-Mehdi ; Degnan, James H. ; Jett, Stephen ; Watt, John ; Escobar, G. Patricia ; Dokladny, Karol ; et al ( December 2023 , Scientific Reports)

   The leitmotifs of magnetic resonance imaging (MRI) contrast agent-induced complications range from acute kidney injury, symptoms associated with gadolinium exposure (SAGE)/gadolinium deposition disease, potentially fatal gadolinium encephalopathy, and irreversible systemic fibrosis. Gadolinium is the active ingredient of these contrast agents, a non-physiologic lanthanide metal. The mechanisms of MRI contrast agent-induced diseases are unknown. Mice were treated with a MRI contrast agent. Human kidney tissues from contrast-naïve and MRI contrast agent-treated patients were obtained and analyzed. Kidneys (human and mouse) were assessed with transmission electron microscopy and scanning transmission electron microscopy with X-ray energy-dispersive spectroscopy. MRI contrast agent treatment resulted in unilamellar vesicles and mitochondriopathy in renal epithelium. Electron-dense intracellular precipitates and the outer rim of lipid droplets were rich in gadolinium and phosphorus. We conclude that MRI contrast agents are not physiologically inert. The long-term safety of these synthetic metal–ligand complexes, especially with repeated use, should be studied further.

    

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4. Exceedingly Small Gadolinium Oxide Nanoparticles with Remarkable Relaxivities for Magnetic Resonance Imaging of Tumors

   https://doi.org/10.1002/smll.201903422  

   Shen, Zheyu ; Fan, Wenpei ; Yang, Zhen ; Liu, Yijing ; Bregadze, Vladimir I. ; Mandal, Swadhin K. ; Yung, Bryant C. ; Lin, Lisen ; Liu, Ting ; Tang, Wei ; et al ( August 2019 , Small)

   Gd chelates have occupied most of the market of magnetic resonance imaging (MRI) contrast agents for decades. However, there have been some problems (nephrotoxicity, non‐specificity, and lowr₁) that limit their applications. Herein, a wet‐chemical method is proposed for facile synthesis of poly(acrylic acid) (PAA) stabilized exceedingly small gadolinium oxide nanoparticles (ES‐GON‐PAA) with an excellent water dispersibility and a size smaller than 2.0 nm, which is a powerfulT₁‐weighted MRI contrast agent for diagnosis of diseases due to its remarkable relaxivities (r₁= 70.2 ± 1.8 mM⁻¹s⁻¹, andr₂/r₁= 1.02 ± 0.03, at 1.5 T). Ther₁is much higher and ther₂/r₁is lower than that of the commercial Gd chelates and reported gadolinium oxide nanoparticles (GONs). Further ES‐GON‐PAA is developed with conjugation of RGD2 (RGD dimer) (i.e., ES‐GON‐PAA@RGD2) forT₁‐weighted MRI of tumors that overexpress RGD receptors (i.e., integrinα_vβ₃). The maximum signal enhancement (ΔSNR) forT₁‐weighted MRI of tumors reaches up to 372 ± 56% at 2 h post‐injection of ES‐GON‐PAA@RGD2, which is much higher than commercial Gd‐chelates (<80%). Due to the high biocompatibility and high tumor accumulation, ES‐GON‐PAA@RGD2 with remarkable relaxivities is a promising and powerfulT₁‐weighted MRI contrast agent.

    

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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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