Niobium oxide exists in several crystal phases and valence states, yielding a variety of properties. Phase transitions between polymorphs significantly alter the properties of functional niobium oxide nanostructures, which are applied in many different renewable energy applications. This study uses environmental transmission electron microscopy to investigate the oxidation of NbO nanowires to T-Nb2O5. Small oxygen partial pressures (<1 mbar) suffice to initiate the oxidation which initially causes the destruction of the lattice ordering prior to the crystallization of the new phase. Different oxygen partial pressures and temperatures are used to manipulate the reaction kinetics. The crystallization is slow at room temperature and confined to the nanowire surface. Elevated temperatures accelerate the crystallization, resulting in the transformation of the complete nanowire. The transformation proceeds via dislocations, yielding the woven-like structure of the transformed nanowire. Despite the dramatic changes of the atomic composition of the material, an orientation relationship between the different phases is preserved. The phase transformation of NbO to T-Nb2O5 observed in situ complies with ex situ phase diagrams. This illustrates the importance of environmental transmission electron microscopy for the investigation of oxidation and reduction reactions of metal oxide nanostructures to identify the impact of shape and intrinsic defects.

Non-rutile polymorphs of binary iridium oxide such as columbite IrO2 (α-IrO2) are promising candidates for highly active acid-stable oxygen evolution reaction (OER) catalysts, yet their synthesis has been challenging due to the dominant thermodynamic stability of rutile IrO2 (R-IrO2). Here, we report the growth of α-IrO2 via epitaxial thin films using pulsed laser deposition. We observe that, in competition with R-IrO2 (100), the films can be optimized to be predominantly (100)-oriented α-IrO2. Surprisingly, the activity of α-IrO2 shows a large discrepancy of ∼0.2 V in the overpotential compared to its predicted activity, which is resolved via theoretical calculations to be a crystal orientation effect. This demonstrates that the electrocatalytic activity can be significantly varied upon crystal orientation, a parameter that is difficult to control in conventional polycrystalline systems but accessible in epitaxial thin films. In total, this study demonstrates epitaxial thin film growth as a powerful technique, which can overcome large energetic instabilities on the order of ∼300 meV to stabilize metastable material structures inaccessible by bulk synthesis. This provides unique opportunities to effectively identify the atomic structure of active catalysts by combining investigations of metastable materials with theoretical predictions.

Elastic strain is being increasingly employed to enhance the catalytic properties of mixed ion-electron conducting oxides. However, its effect on oxygen storage capacity is not well established. Here, we fabricate ultrathin, coherently strained films of CeO_2-δ between 5.6% biaxial compression and 2.1% tension. In situ ambient pressure X-ray photoelectron spectroscopy reveals up to a fourfold enhancement in equilibrium oxygen storage capacity under both compression and tension. This non-monotonic variation with strain departs from the conventional wisdom based on a chemical expansion dominated behaviour. Through depth profiling, film thickness variations and a coupled photoemission-thermodynamic analysis of space-charge effects, we show that the enhanced reducibility is not dominated by interfacial effects. On the basis of ab initio calculations of oxygen vacancy formation incorporating defect interactions and vibrational contributions, we suggest that the non-monotonicity arises from the tetragonal distortion under large biaxial strain. These results may guide the rational engineering of multilayer and core-shell oxide nanomaterials.

Increasing cell survival in stem cell therapy is an important challenge for the field of regenerative medicine. Here, we report theranostic mesoporous silica nanoparticles that can increase cell survival through both diagnostic and therapeutic approaches. First, the nanoparticle offers ultrasound and MRI signal to guide implantation into the peri-infarct zone and away from the most necrotic tissue. Second, the nanoparticle serves as a slow release reservoir of insulin-like growth factor (IGF)-a protein shown to increase cell survival. Mesenchymal stem cells labeled with these nanoparticles had detection limits near 9000 cells with no cytotoxicity at the 250 µg/mL concentration required for labeling. We also studied the degradation of the nanoparticles and showed that they clear from cells in approximately 3 weeks. The presence of IGF increased cell survival up to 40% (p<0.05) versus unlabeled cells under in vitro serum-free culture conditions.

The growing use of nanoparticles in biomedical applications, including cancer diagnosis and treatment, demands the capability to exactly locate them within complex biological systems. In this work a correlative optical and scanning electron microscopy technique was developed to locate and observe multi-modal gold core nanoparticle accumulation in brain tumor models. Entire brain sections from mice containing orthotopic brain tumors injected intravenously with nanoparticles were imaged using both optical microscopy to identify the brain tumor, and scanning electron microscopy to identify the individual nanoparticles. Gold-based nanoparticles were readily identified in the scanning electron microscope using backscattered electron imaging as bright spots against a darker background. This information was then correlated to determine the exact location of the nanoparticles within the brain tissue. The nanoparticles were located only in areas that contained tumor cells, and not in the surrounding healthy brain tissue. This correlative technique provides a powerful method to relate the macro- and micro-scale features visible in light microscopy with the nanoscale features resolvable in scanning electron microscopy.

Nanoparticles' enhanced permeation and retention (EPR) variations due to tumor heterogeneity in naturally occurring brain tumors are commonly neglected in preclinical nanomedicine studies. Recent pathological studies have shown striking similarities between brain tumors in humans and dogs, indicating that canine brain tumors may be a valuable model to evaluate nanoparticles' EPR in this context. We recruited canine clinical cases with spontaneous brain tumors to investigate nanoparticles' EPR in different brain tumor pathologies using surface-enhanced Raman spectroscopy (SERS). We used gold nanoparticles due to their surface plasmon effect that enables their sensitive and microscopic resolution detection using the SERS technique. Raman microscopy of the resected tumors showed heterogeneous EPR of nanoparticles into oligodendrogliomas and meningiomas of different grades, without any detectable traces in necrotic parts of the tumors or normal brain. Raman observations were confirmed by scanning electron microscopy (SEM) and X-ray elemental analyses, which enabled localization of individual nanoparticles embedded in tumor tissues. Our results demonstrate nanoparticles' EPR and its variations in clinically relevant, spontaneous brain tumors. Such heterogeneities should be considered alongside routine preoperative imaging and histopathological analyses in order to accelerate clinical management of brain tumors using nanomedicine approaches.

Increasing the energy density of layered oxide battery electrodes is challenging as accessing high states of delithiation often triggers voltage degradation and oxygen release. Here we utilize transmission-based X-ray absorption spectromicroscopy and ptychography on mechanically cross-sectioned Li1.18–xNi0.21Mn0.53Co0.08O2–δ electrodes to quantitatively profile the oxygen deficiency over cycling at the nanoscale. The oxygen deficiency penetrates into the bulk of individual primary particles (~200 nm) and is well-described by oxygen vacancy diffusion. Using an array of characterization techniques, we demonstrate that, surprisingly, bulk oxygen vacancies that persist within the native layered phase are indeed responsible for the observed spectroscopic changes. We additionally show that the arrangement of primary particles within secondary particles (~5 μm) causes considerable heterogeneity in the extent of oxygen release between primary particles. Our work merges an ensemble of length-spanning characterization methods and informs promising approaches to mitigate the deleterious effects of oxygen release in lithium-ion battery electrodes.

Background

Anthracycline-induced cardiomyopathy (AIC) is a significant source of morbidity and mortality in cancer survivors. The role of mesenchymal stem cells (MSCs) in treating AIC was evaluated in the SENECA trial, a Phase 1 National Heart, Lung, and Blood Institute-sponsored study, but the mechanisms underpinning efficacy in human tissue need clarification.

Objectives

The purpose of this study was to perform an in vitro clinical trial evaluating the efficacy and putative mechanisms of SENECA trial-specific MSCs in treating doxorubicin (DOX) injury, using patient-specific induced pluripotent stem cell-derived cardiomyocytes (iCMs) generated from SENECA patients.

Methods

Patient-specific iCMs were injured with 1 μmol/L DOX for 24 hours, treated with extracellular vesicles (EVs) from MSCs by either coculture or direct incubation and then assessed for viability and markers of improved cellular physiology. MSC-derived EVs were separated into large extracellular vesicles (L-EVs) (>200 nm) and small EVs (<220nm) using a novel filtration system.

Results

iCMs cocultured with MSCs in a transwell system demonstrated improved iCM viability and attenuated apoptosis. L-EVs but not small EVs recapitulated this therapeutic effect. L-EVs were found to be enriched in mitochondria, which were shown to be taken up by iCMs. iCMs treated with L-EVs demonstrated improved contractility, reactive oxygen species production, ATP production, and mitochondrial biogenesis. Inhibiting L-EV mitochondrial function with 1-methyl-4-phenylpyridinium attenuated efficacy.

Conclusions

L-EV-mediated mitochondrial transfer mitigates DOX injury in patient-specific iCMs. Although SENECA was not designed to test MSC efficacy, consistent tendencies toward a positive effect were observed across endpoints. Our results suggest a mechanism by which MSCs may improve cardiovascular performance in AIC independent of regeneration, which could inform future trial design evaluating the therapeutic potential of MSCs.