The use of focused ultrasonic waves to modulate neural structures has gained recent interest due to its potential in treating neurological disorders non-invasively. While several papers have focused on the use of ultrasound neuromodulation on peripheral nerves, none of these studies have been performed on the vagus nerve. We present preliminary observations on the effects of focused pulsed ultrasound (FPUS) on the conduction of the left cervical vagus nerve of a Long Evans rat. Ultrasound energy was applied at a frequency of 1.1 MHz, and at spatial-peak, temporal average intensities that ranged from 13.6 to 93.4 W/cm2. Vagus nerve inhibition was observed in most cases. Results of this preliminary study suggested that there is a proportional relationship between acoustic intensity and the level of nerve inhibition.
Hyperthermia has been investigated as a potential treatment for cancer. However, specificity in hyperthermia application remains a significant challenge. Magnetic fluid hyperthermia (MFH) may be an alternative to surpass such a challenge, but implications of MFH at the cellular level are not well understood. Therefore, the present work focused on the examination of gene expression after MFH treatment and using such information to identify target genes that when inhibited could produce an enhanced therapeutic outcome after MFH. Genomic analyzes were performed using ovarian cancer cells exposed to MFH for 30 minutes at 43°C, which revealed that heat shock protein (HSP) genes, including , were upregulated. encodes the Hsp70, and its expression was confirmed by PCR in HeyA8 and A2780cp20 ovarian cancer cells. Two strategies were investigated to inhibit Hsp70-related genes, siRNA and Hsp70 protein function inhibition by 2-phenylethyenesulfonamide (PES). Both strategies resulted in decreased cell viability following exposure to MFH. Combination index was calculated for PES treatment reporting a synergistic effect. efficacy experiments with siRNA and MFH were performed using the A2780cp20 and HeyA8 ovarian cancer mouse models. A significantly reduction in tumor growth rate was observed with combination therapy. PES and MFH efficacy were also evaluated in the HeyA8 intraperitoneal tumor model, and resulted in robust antitumor effects. This work demonstrated that HSP70 inhibition combination with MFH generate a synergistic effect and could be a promising target to enhance MFH therapeutic outcomes in ovarian cancer. .
Iron oxide nanoparticles were coated with the biocompatible, biodegradable, non-immunogenic polysaccharide inulin by introduction of carboxyl groups into the inulin structure and conjugation with amine groups on the surface of iron oxide nanoparticles grafted with 3-aminopropyltriethoxysilane. The resulting nanoparticles were characterized by FT-IR spectroscopy, transmission electron microscopy, dynamic light scattering, zeta potential, SQUID magnetometry, and with respect to their energy dissipation rate in applied alternating magnetic fields. The nanoparticles had a hydrodynamic diameter in the range of 70 ± 10 nm and were superparamagnetic, with energy dissipation rates in the range of 58–175 W/g for an applied field frequency of 233 kHz and an applied field amplitude in the range of 20–48 kA/m. The nanoparticles were stable in a range of pH, at temperatures between 23°C and 53°C, and in short term storage in water, PBS, and culture media. The particles were non-cytotoxic to the immortalized human cancer cell lines Hey A8 FDR, A2780, MDA 468, MCF-7 and Caco-2. The nanoparticles were readily taken up by Caco-2 cells in a time and concentration dependent fashion, and were found to have a pharmacokinetic time constant of 47 ± 3 min. The small size, non-cytotoxicity, and efficient energy dissipation of the particles could make them useful for biomedical applications such as magnetic fluid hyperthermia.
Multifunctional nanoparticles show great potential in the biomedical field and may help the diagnosis and therapy of diseases. Superparamagnetic nanoparticles are especially attractive because of their ability to dissipate thermal energy in an alternating magnetic field. Furthermore, plasmonic nanoparticles can be effectively used in non- or minimally invasive therapy of tumors exploiting their plasmonic photothermal effect. Here, hybrid plasmonic-magnetic Ag/Fe2O3 nanoparticles are made by flame aerosol technology. These nanoparticles can be in situ encapsulated with an amorphous nanothin SiO2 film to facilitate their dispersion and block any toxicity from Ag/Fe2O3. Detailed physicochemical characterization, including electron microscopy, electron dispersive X-ray spectroscopy, and X-ray diffraction, is performed. Furthermore, their magnetic properties are characterized in detail by monitoring their hysteresis, first-order-reversal-curves, and isothermal remanent magnetization. Finally, the effect of SiO2 and Ag-content on the specific absorption rate (SAR) of the hybrid Ag/Fe2O3 nanoparticles is investigated. The obtained understanding will help the rational design and engineering of multifunctional hybrid nanoprobes targeting specific biomedical applications.
Background: Magnetic Fluid Hyperthermia (MFH) is a promising adjuvant for chemotherapy, potentiating the action of anticancer agents. However, drug delivery to cancer cells must be optimized to improve the overall therapeutic effect of drug/MFH combination treatments. Purpose: The aim of this work was to demonstrate the potentiation of 2-phenylethynesulfonamide (PES) at various combination treatments with MFH, using low-intensity ultrasound as an intracellular delivery enhancer. Methods: The effect of ultrasound (US), MFH, and PES was first evaluated individually and then as combination treatments. Definity ® microbubbles and polyethylene glycol (PEG)-coated iron oxide nanoparticles were used to induce cell sonoporation and MFH, respectively. Assessment of cell membrane permeabilization was evaluated via fluorescence microscopy, iron uptake by cells was quantified by UV-Vis spectroscopy, and cell viability was determined using automatic cell counting. Results: Notable reductions in cancer cell viability were observed when ultrasound was incorporated. For example, the treatment US+PES reduced cell viability by 37% compared to the non-toxic effect of the drug. Similarly, the treatment US+MFH using mild hyperthermia (41°C), reduced cell viability by an additional 18% when compared to the effect of MH alone. Significant improvements were observed for the combination of US+PES+MFH with cell viability reduced by an additional 26% compared to the PES+MFH group. The improved cytotoxicity was attributed to enhanced drug/nanoparticle intracellular delivery, with iron uptake values nearly twice those achieved without ultrasound. Various treatment schedules were examined, and all of them showed substantial cell death, indicating that the time elapsed between sonoporation and magnetic field exposure was not significant. Conclusion: Superior cancer cell-killing patterns took place when ultrasound was incorporated thus demonstrating the in vitro ultrasonic potentiation of PES and mild MFH. This work demonstrated that ultrasound is a promising non-invasive enhancer of PES/MFH combination treatments, aiming to establish a sono-thermo-chemotherapy in the treatment of ovarian cancer.
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