Extrusion: A New Method for Rapid Formulation of High-Yield, Monodisperse Nanobubbles

Shell-stabilized gas microbubbles (MB) and nanobubbles (NB) are frequently used for biomedical ultrasound imaging and therapeutic applications. While it is widely recognized that monodisperse bubbles can be more effective in these applications, the efficient formulation of uniform bubbles at high concentrations is difficult to achieve. Here, it is demonstrated that a standard mini-extruder setup, commonly used to make vesicles or liposomes, can be used to quickly and efficiently generate monodisperse NBs with high yield. In this highly reproducible technique, the NBs obtained have an average diameter of 0.16 ± 0.05 µm and concentration of 6.2 ± 1.8 × 1010 NBs mL−1 compared to 0.32 ± 0.1 µm and 3.2 ± 0.7 × 1011 mL−1 for NBs made using mechanical agitation. Parameters affecting the extrusion and NB generation process including the temperature, concentration of the lipid solution, and the number of passages through the extruder are also examined. Moreover, it is demonstrated that extruded NBs show a strong acoustic response in vitro and a strong and persistent US signal enhancement under nonlinear contrast enhanced ultrasound imaging in mice. The extrusion process is a new, efficient, and scalable technique that can be used to easily produce high yield smaller monodispersed nanobubbles

Surface energies of magnetic recording head components

The rate of material removal during fixed abrasive lapping is a function of friction coefficient, the surface tension of the lubricant and of the substrate, and the contact angles between the interfaces. In this study, the authors measured the surface energies of materials typically found in thin film magnetic recording heads using contact angle measurements and the Lifshitz–van der Waals acid/base approach. The different materials tested were NixFey, Al2O3, and Al2O3-TiC. Sample preparation procedures were also considered. The chemical used to wash the surface was observed to affect the measured substrate surface energies. Surface energy values for samples washed with either acetone or hexane showed comparable results. The NixFey gave the highest measured surface energy (46.3–48.8 mJ m−2) followed by Al2O3 (44.1–45.3 mJ m−2) and Al2O3-TiC (43.3–45.3 mJ m−2). In contrast, the oil-washed samples measured generally lower surface energy values. The study characterized the interaction of two lubricant types against the three materials. The oil-based lubricant spreads completely on oil-washed samples mainly because of the low surface tension of the oil (22.0 mJ m−2) and did not show measurable contact angles. In comparison, the water-soluble lubricant ethylene glycol, due to its higher surface tension (48.0 mJ m−2), formed higher contact angles ranging from 47.2 to 59.6° on the different substrates

Structural effects on the magnetic hyperthermia properties of iron oxide nanoparticles

AbstractMagnetic iron oxide nanoparticles (IONPs) are heavily explored as diagnostic and therapeutic agents due to their low cost, tunable properties, and biocompatibility. In particular, upon excitation with an alternating current (AC) magnetic field, the NPs generate localized heat that can be exploited for therapeutic hyperthermia treatment of diseased cells or pathogenic microbes. In this review, we focus on how structural changes and inter-particle interactions affect the heating efficiency of iron oxide-based magnetic NPs. Moreover, we present an overview of the different approaches to evaluate the heating performance of IONPs and introduce a new theranostic modality based on magnetic imaging guided–hyperthermia

Ultrasound-Based Molecular Imaging of Tumors with PTPmu Biomarker-Targeted Nanobubble Contrast Agents

Ultrasound imaging is a widely used, readily accessible and safe imaging modality. Molecularly-targeted microbubble- and nanobubble-based contrast agents used in conjunction with ultrasound imaging expand the utility of this modality by specifically targeting and detecting biomarkers associated with different pathologies including cancer. In this study, nanobubbles directed to a cancer biomarker derived from the Receptor Protein Tyrosine Phosphatase mu, PTPmu, were evaluated alongside non-targeted nanobubbles using contrast enhanced ultrasound both in vitro and in vivo in mice. In vitro resonant mass and clinical ultrasound measurements showed gas-core, lipid-shelled nanobubbles conjugated to either a PTPmu-directed peptide or a Scrambled control peptide were equivalent. Mice with heterotopic human tumors expressing the PTPmu-biomarker were injected with PTPmu-targeted or control nanobubbles and dynamic contrast-enhanced ultrasound was performed. Tumor enhancement was more rapid and greater with PTPmu-targeted nanobubbles compared to the non-targeted control nanobubbles. Peak tumor enhancement by the PTPmu-targeted nanobubbles occurred within five minutes of contrast injection and was more than 35% higher than the Scrambled nanobubble signal for the subsequent two minutes. At later time points, the signal in tumors remained higher with PTPmu-targeted nanobubbles demonstrating that PTPmu-targeted nanobubbles recognize tumors using molecular ultrasound imaging and may be useful for diagnostic and therapeutic purposes

Iron Oxide and Titanium Dioxide Nanoparticle Effects on Plant Performance and Root Associated Microbes

In this study, we investigated the effect of positively and negatively charged Fe3O4 and TiO2 nanoparticles (NPs) on the growth of soybean plants (Glycine max.) and their root associated soil microbes. Soybean plants were grown in a greenhouse for six weeks after application of different amounts of NPs, and plant growth and nutrient content were examined. Roots were analyzed for colonization by arbuscular mycorrhizal (AM) fungi and nodule-forming nitrogen fixing bacteria using DNA-based techniques. We found that plant growth was significantly lower with the application of TiO2 as compared to Fe3O4 NPs. The leaf carbon was also marginally significant lower in plants treated with TiO2 NPs; however, leaf phosphorus was reduced in plants treated with Fe3O4. We found no effects of NP type, concentration, or charge on the community structure of either rhizobia or AM fungi colonizing plant roots. However, the charge of the Fe3O4 NPs affected both colonization of the root system by rhizobia as well as leaf phosphorus content. Our results indicate that the type of NP can affect plant growth and nutrient content in an agriculturally important crop species, and that the charge of these particles influences the colonization of the root system by nitrogen-fixing bacteria

Formulation of a Thermosensitive Imaging Hydrogel for Topical Application and Rapid Visualization of Tumor Margins in the Surgical Cavity

Background: Tumor-positive surgical margins during primary breast cancer (BCa) surgery are associated with a two-fold increase in the risk of local recurrence when compared with tumor-negative margins. Pathological microscopic evaluation of the samples only assesses about 1/10 of 1% of the entire volume of the removed BCa specimens, leading to margin under-sampling and potential local recurrence in patients with pathologically clean margins, i.e., false negative margins. In the case of tumor-positive margins, patients need to undergo re-excision and/or radiation therapy, resulting in increases in complications, morbidity, and healthcare costs. Development of a simple real-time imaging technique to identify residual BCa in the surgical cavity rapidly and precisely could significantly improve the quality of care. Methods: A small-molecule, fluorescently quenched protease-substrate probe, AKRO-QC-ICG, was tested as part of a thermosensitive imaging gel formulated for topical application and imaging of the BCa surgical cavity. Results: More than forty formulations of gel mixtures were investigated to enable easy fluid application and subsequent solidification once applied, preventing dripping and pooling in the surgical cavity. The final formulation was tested using human BCa orthotopic implants in nude and NSG patient-derived xenografts (PDX) mice. This formulation of Pluronic F-127/DMSO/AKRO-QC-ICG imaging gel was found to be a good solvent for the probe, with a desirable thermo-reversible solid–gel transition and mechanical strength for distribution of AKRO-QC-ICG on the surfaces of tissue. It demonstrated excellent ability to detect BCa tissue after 10 min exposure, with a high signal-to-noise ratio both in mouse xenografts and freshly excised human lumpectomy tissue. The in vivo efficacy of the AKRO-QC-ICG imaging gel to detect BCa revealed the levels of sensitivity/specificity = 0.92/1 in 12 nude mice, which was corroborated with the sensitivity/specificity = 0.94/1 in 10 PDX mice. Conclusions: Utilization of Pluronic F-127/DMSO/AKRO-QC-ICG imaging gel for topical application to detect BCa in the surgical cavity during surgery has the potential to reduce re-excisions, with consequent savings in healthcare costs and enhancement in patient quality of life

Magnetic Glycol Chitin-Based Hydrogel Nanocomposite for Combined Thermal and d‑Amino-Acid-Assisted Biofilm Disruption

Bacterial biofilms are highly antibiotic resistant microbial cell associations that lead to chronic infections. Unlike free-floating planktonic bacterial cells, the biofilms are encapsulated in a hardly penetrable extracellular polymeric matrix and, thus, demand innovative approaches for treatment. Recent advancements on the development of gel-nanocomposite systems with tailored therapeutic properties provide promising routes to develop novel antimicrobial agents that can be designed to disrupt and completely eradicate preformed biofilms. In our study, we developed a unique thermoresponsive magnetic glycol chitin-based nanocomposite containing d-amino acids and iron oxide nanoparticles, which can be delivered and undergoes transformation from a solution to a gel state at physiological temperature for sustained release of d-amino acids and magnetic field actuated thermal treatment of targeted infection sites. The d-amino acids in the hydrogel nanocomposite have been previously reported to inhibit biofilm formation and also disrupt existing biofilms. In addition, loading the hydrogel nanocomposite with magnetic nanoparticles allows for combination thermal treatment following magnetic field (magnetic hyperthermia) stimulation. Using this novel two-step approach to utilize an externally actuated gel-nanocomposite system for thermal treatment, following initial disruption with d-amino acids, we were able to demonstrate in vitro the total eradication of <i>Staphylococcus aureus</i> biofilms, which were resistant to conventional antibiotics and were not completely eradicated by separate d-amino acid or magnetic hyperthermia treatments