Mayra Hernández-Rivera

Bismuth@US-tubes as a potential contrast agent for X-ray imaging applications

The encapsulation of bismuth as BiOCl/Bi2O3 within ultra-short (ca. 50 nm) single-walled carbon nanocapsules (US-tubes) has been achieved. The Bi@US-tubes have been characterized by high-resolution transmission electron microscopy (HR-TEM), energy-dispersive X-ray spectroscopy (EDS), thermogravimetric analysis (TGA), X-ray photoelectron spectroscopy (XPS), and Raman spectroscopy. Bi@US-tubes have been used for intracellular labeling of pig bone marrow-derived mesenchymal stem cells (MSCs) to show high X-ray contrast in computed tomography (CT) cellular imaging for the first time. The relatively high contrast is achieved with low bismuth loading (2.66% by weight) within the US-tubes and without compromising cell viability. X-ray CT imaging of Bi@US-tubes-labeled MSCs showed a nearly two-fold increase in contrast enhancement when compared to unlabeled MSCs in a 100 kV CT clinical scanner. The CT signal enhancement from the Bi@US-tubes is 500 times greater than polymer-coated Bi2S3 nanoparticles and several-fold that of any clinical iodinated contrast agent (CA) at the same concentration. Our findings suggest that the Bi@US-tubes can be used as a potential new class of X-ray CT agent for stem cell labeling and possibly in vivo tracking.

The use of gadolinium-carbon nanostructures to magnetically enhance stem cell retention for cellular cardiomyoplasty.

In this work, the effectiveness of using Gadonanotubes (GNTs) with an external magnetic field to improve retention of transplanted adult mesenchymal stem cells (MSCs) during cellular cardiomyoplasty was evaluated. As a high-performance T1-weighted magnetic resonance imaging (MRI) cell tracking label, the GNTs are gadolinium-loaded carbon nanotube capsules that render MSCs magnetic when internalized. MSCs were internally labeled with either superparamagnetic GNTs or colloidal diamagnetic lutetium (Lu). In vitro cell rolling assays and ex vivo cardiac perfusion experiments qualitatively demonstrated increased magnetic-assisted retention of GNT-labeled MSCs. Subsequent in vivo epicardial cell injections were performed around a 1.3 T NdFeB ring magnet sutured onto the left ventricle of female juvenile pigs (n = 21). Cell dosage, magnet exposure time, and endpoints were varied to evaluate the safety and efficacy of the proposed therapy. Quantification of retained cells in collected tissues by elemental analysis (Gd or Lu) showed that the external magnet helped retain nearly three times more GNT-labeled MSCs than Lu-labeled cells. The sutured magnet was tolerated for up to 168 h; however, an inflammatory response to the magnet was noted after 48 h. These proof-of-concept studies support the feasibility and value of using GNTs as a magnetic nanoparticle facilitator to improve cell retention during cellular cardiomyoplasty.

Three-dimensional solvent-vapor map generated by supramolecular metal-complex entrapment.

Supramolecular assemblies have become increasingly popular over the past few years, especially in areas such as catalysis, gas sequestration, and separation. Similarly, interesting approaches for the detection of toxic gases and vapors of volatile organic compounds (VOCs) have been studied to develop an artificial nose that is capable of identifying these species in an unambiguous and simple way. The use of supramolecular and crystalline arrays of metal complexes with electronic transitions that are sensitive to the presence of a variety of volatile molecules, has received considerable attention. However, although metal complexes of platinum, gold, palladium, and copper have been widely employed for vapor detection, rhenium has been rarely used. Herein, we propose to use a zeolite framework for the supramolecular assembly of rhenium complexes with applications to vapor sensing. Zeolites are aluminosilicates with a repeating microporous structure composed of {AlO4} and {SiO4} building blocks. The internal framework is a network of cavities (supercages) that are interconnected by channels (Figure 1a). This architecture allows zeolites to act as molecular sieves, with applications ranging from catalysis to light-harvesting systems. Because of their porous structure, ion-exchange properties, and molecular and size recognition, many ions and molecules have been immobilized within zeolites. Particularly relevant for this research, the photoluminescent tris(2,2’-bipyridine)ruthenium(II) complex ([Ru(bpy)3] ) has been encapsulated in NaY and thoroughly studied. As the pore diameter of the NaY framework is smaller than the diameter of [Ru(bpy)3] , this molecule is synthesized in situ by a ship-in-the-bottle method. This method involves the loading of NaY with a ruthenium salt, followed by the addition of 2,2’-bipyridine as a ligand. The [Ru(bpy)3] 2+ complex is formed inside the supercage, and therefore it becomes entrapped within the zeolite. The material is fundamentally composed of a zeolite framework, with the supercages occupied by individual [Ru(bpy)3] 2+ ions, thus forming a true solid solution. Inspired by the aforementioned reports, we used the shipin-the-bottle method to synthesize [Re(phen)(CO)3Cl] (phen= 1,10-phenanthroline) in the cavities of the NaY zeolite. The ligands and the metal react in the NaY supercages to form the [Re(phen)(CO)3Cl] complex. The supercages of the NaY zeolite have a diameter of approximately 13 (large enough to accommodate the complex with a diameter of ca. 9 ) and pore entrances of approximately 7.4 . Therefore, the rhenium complex can fit into the supercage, but once it has been entrapped inside, it is too large to diffuse out of the cage through the pore entrance. To the best of our knowledge, Figure 1. Effect of solvent vapors on the photophysical properties of [Re(phen)(CO)3Cl]@NaY. a) Representation of the NaY zeolite showing one of the supercavities where [Re(phen)(CO)3Cl] can be entrapped. b) Photoluminescence spectra of [Re(phen)(CO)3Cl]@NaY upon treatment with different solvent vapors showing the change in emission intensity (no vapor: material before exposure to vapor, with a photoluminescence adjusted to unity). c) The normalized photoluminescence, which was obtained from the spectra in (b), emphasizes the change in photoluminescence maxima with different vapors. d) Timeresolved photoluminescence decays of [Re(phen)(CO)3Cl]@NaY under different solvent vapors. e) Digital photographs of vapor-treated [Re(phen)(CO)3Cl]@NaYmaterial under UV light. DMF=N,N-dimethylformamide, DMSO=dimethyl sulfoxide.

High-Performance Hybrid Bismuth-Carbon Nanotube Based Contrast Agent for X-ray CT Imaging

Carbon nanotubes (CNTs) have been used for a plethora of biomedical applications, including their use as delivery vehicles for drugs, imaging agents, proteins, DNA, and other materials. Here, we describe the synthesis and characterization of a new CNT-based contrast agent (CA) for X-ray computed tomography (CT) imaging. The CA is a hybrid material derived from ultrashort single-walled carbon nanotubes (20-80 nm long, US-tubes) and Bi(III) oxo-salicylate clusters with four Bi(III) ions per cluster (Bi4C). The element bismuth was chosen over iodine, which is the conventional element used for CT CAs in the clinic today due to its high X-ray attenuation capability and its low toxicity, which makes bismuth a more-promising element for new CT CA design. The new CA contains 20% by weight bismuth with no detectable release of bismuth after a 48 h challenge by various biological media at 37 °C, demonstrating the presence of a strong interaction between the two components of the hybrid material. The performance of the new Bi4C@US-tubes solid material as a CT CA has been assessed using a clinical scanner and found to possess an X-ray attenuation ability of >2000 Hounsfield units (HU).

Eliminating Nox2 reactive oxygen species production protects dystrophic skeletal muscle from pathological calcium influx assessed in vivo by manganese‐enhanced magnetic resonance imaging

Inhibiting Nox2 reactive oxygen species (ROS) production reduced in vivo calcium influx in dystrophic muscle. The lack of Nox2 ROS production protected against decreased in vivo muscle function in dystrophic mice. Manganese‐enhanced magnetic resonance imaging (MEMRI) was able to detect alterations in basal calcium levels in skeletal muscle and differentiate disease status. Administration of Mn2+ did not affect muscle function or the health of the animal, and Mn2+ was cleared from skeletal muscle rapidly. We conclude that MEMRI may be a viable, non‐invasive technique to monitor molecular alterations in disease progression and evaluate the effectiveness of potential therapies for Duchenne muscular dystrophy.

Eliminating Nox2 ROS production protects dystrophic skeletal muscle from pathological calcium influx assessed in vivo by manganese enhanced MRI

Inhibiting Nox2 reactive oxygen species (ROS) production reduced in vivo calcium influx in dystrophic muscle. The lack of Nox2 ROS production protected against decreased in vivo muscle function in dystrophic mice. Manganese‐enhanced magnetic resonance imaging (MEMRI) was able to detect alterations in basal calcium levels in skeletal muscle and differentiate disease status. Administration of Mn2+ did not affect muscle function or the health of the animal, and Mn2+ was cleared from skeletal muscle rapidly. We conclude that MEMRI may be a viable, non‐invasive technique to monitor molecular alterations in disease progression and evaluate the effectiveness of potential therapies for Duchenne muscular dystrophy.

A New High-Performance Gadonanotube-Polymer Hybrid Material for Stem Cell Labeling and Tracking by MRI

A gentle, rapid method has been developed to introduce a polyacrylic acid (PAA) polymer coating on the surface of gadonanotubes (GNTs) which significantly increases their dispersibility in water without the need of a surfactant. As a result, the polymer, with its many carboxylic acid groups, coats the surface of the GNTs to form a new GNT-polymer hybrid material (PAA-GNT) which can be highly dispersed in water (ca. 20 mg·mL−1) at physiological pH. When dispersed in water, the new PAA-GNT material is a powerful MRI contrast agent with an extremely short water proton spin-lattice relaxation time (T 1) which results in a T 1-weighted relaxivity of 150 mM−1·s−1 per Gd3+ ion at 1.5 T. Furthermore, the PAA-GNTs have been used to safely label porcine bone-marrow-derived mesenchymal stem cells for magnetic resonance imaging. The labeled cells display excellent image contrast in phantom imaging experiments, and transmission electron microscopy images of the labeled cells reveal the presence of highly dispersed PAA-GNTs within the cytoplasm with 1014 Gd3+ ions per cell.