Production of local microbubbles (MBs) with dense distribution in tumor environment is achieved by developing an integrated electrochemical stimulator on a microfabricated silicon needle covered by zinc‐oxide nanowires (ZnONWs). MBs are then exploded by external ultrasonic actuation, which induce microcavitations in tumor cells followed by direct entrance of anticancer drugs into cancer cells. This system, named ZnO nanowire‐based microbubble generator probe (ZnONW‐MGP), is tested on tumorized mice models (by MC4L2 breast cell lines). Mice treated by ZnONW‐MGP have ≈82% reduction in tumor size within 10 days with just 25% of conventional dose of paclitaxel while in the absence of the system, they have just a 15% reduction in tumor size. Presence of ZnO nanostructures on microneedles strongly reduces the size of MBs and enhances the efficacy of the sonoporation.
In this research, the flow around the autonomous underwater vehicles with symmetrical bodies is numerically investigated. Increasing the drag force in autonomous underwater vehicles increases the energy consumption and decreases the duration of underwater exploration and operations. Therefore, the main objective of this research is to decrease drag force with the change in geometry to reduce energy consumption. In this study, the decreasing or increasing trends of the drag force of axisymmetric bare hulls have been studied by making alterations in the curve equations and creating the optimal geometric shapes in terms of hydrodynamics for the noses and tails of autonomous underwater vehicles. The incompressible, three-dimensional, and steady Navier–Stokes equations have been used to simulate the flow. Also, k-ε Realizable with enhanced wall treatment was used for turbulence modeling. Validation results were acceptable with respect to the 3.6% and 1.4% difference with numerical and experimental results. The results showed that all the autonomous underwater vehicle hulls designed in this study, at an attack angle of 0°, had a lower drag force than the autonomous underwater vehicle hull used for validation except geometry no. 1. In addition, nose no. 3 has been selected as the best nose according to the lowest value of stagnation pressure, and also tail no. 3 has been chosen as the best tail due to the production of the lowest vortex. Therefore, geometry no. 5 has been designed using nose and tail no. 3. The comparison made here showed that the maximum drag reduction in geometry no. 5 was equal to 26%, and therefore, it has been selected as the best bare hull in terms of hydrodynamics.
Artificial cavitation as a prerequisite of sonoporation, plays an important role on the ultrasound (US) assisted drug delivery systems. In this study, we have proposed a new method of microbubble (MB) generation by local electrolysis of the medium. An integrated interdigital array of three-electrode system was designed and patterned on a nickel-coated quartz substrate and then, a short DC electrical pulse was applied that consequently resulted in distributed generation of microbubbles at the periphery of the electrodes. Growth of the carbon nanotube (CNT) nanostructures on the surface of the electrodes approximately increased the number of generated microbubbles up to 7-fold and decreased their average size from ∼20 µm for bare to ∼7 µm for CNT electrodes. After optimizing the three-electrode system, biocompatibility assays of the CNT electrodes stimulated by DC electrical micropulses were conducted. Finally, the effect of the proposed method on the sonoporation efficiency and drug uptake of breast cells were assessed using cell cycle and Annexin V/PI flow cytometry analysis. These results show the potential of electrochemical generation of MBs by CNT electrodes as an easy, available and promising technique for artificial cavitation and ultrasound assisted drug delivery.
It is increasingly being accepted that cells' physiological functions are substantially dependent on the mechanical characteristics of their surrounding tissue. This is mainly due to the key role of biomechanical forces on cells and their nucleus' shapes, which have the capacity to regulate chromatin conformation and thus gene regulations. Therefore, it is reasonable to postulate that altering the biomechanical properties of tissue may have the capacity to change cell functions. Here, the role of cell stretching (as a model of biomechanical variations) is probed in cell migration and invasion capacity using human normal and cancerous breast cells. By several analyses (i.e., scratch assay, invasion to endothelial barrier, real‐time RNA sequencing, confocal imaging, patch clamp, etc.), it is revealed that the cell‐stretching process could increase the migration and invasion capabilities of normal and cancerous cells, respectively. More specifically, it is found that poststretched breast cancer cells are found in low grades of invasion; they substantially upregulate the expression of manganese‐dependent superoxide dismutase (MnSOD) through activation of H‐Ras proteins, which subsequently induce aerobic glycolysis followed by an overproduction of matrix metalloproteinases (MMP)‐reinforced filopodias. Presence of such invadopodias facilitates targeting of the endothelial layer, and increased invasive behaviors in breast cells are observed.
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