Ultrasonic exposure enhances the body’s antioxidant capacity

Introduction: Nowadays, the applications of non-invasive treating cancer methods such as photothermal therapy (PTT) and sonodynamic therapy (SDT) are increasing. These treatments use photo/sonosensitizers, which are activated after being exposed by laser light irradiation and ultrasound (US) exposure, respectively. Methods: Herein, a gold-poly (ortho-aminophenol) nanocomposite (Au-PoAP NC) with a spherical shape, a diameter of 46±8 nm was synthesized and evaluated as an 808-nm laser photosensitizer (with 30% photothermal efficiency) and a sonosensitizer upon US exposure. Additionally, Au-PoAP NC was appraised with doxorubicin (as a chemotherapy agent) for treating breast cancer cells. The MTT test was done for celltoxicity evaluation of Au-PoAP NC, doxorubicin, and Au-PoAP NC with doxorubicin with or without irradiation and US exposure (separately and synchronously). The results proved that light irradiation and US exposure (separately and synchronously) of Au-PoAP NC with doxorubicin significantly enhanced the cell toxicity in other treatment groups. Moreover, cytotoxicity of Au-PoAP NC, doxorubicin, and Au-PoAP NC with doxorubicin toward MCF-7 cells upon PTT and/or SDT was investigated from the aspect of reactive oxygen species (ROS) formation. Calculating the combination indices revealed that synchronous administration of Au-PoAP NC and doxorubicin and light irradiation and US exposure represented a synergistic therapeutic manner for treating cancer cells. This study proved that the synchronous combination of PTT and SDT using Au-PoAP NC with doxorubicin would be an exemplary approach for treating the breast cancer cell line of MCF-7.

We have previously developed laminin-derived AG73 peptide-labeled poly(ethylene glycol)-modified liposomes (AG73-PEG liposomes) for selective cancer gene therapy and reported that Bubble liposomes (BLs) and ultrasound (US) exposure could accelerate the endosomal escape of AG73-PEG liposomes, leading to the enhancement of transfection efficiency; however, it is still unclear whether BLs and US exposure can also enhance the transfection efficiency of other vectors. We therefore assessed the effect of BLs and US exposure on the gene transfection efficiency of trans-activating transcriptor (TAT) peptide modified PEG liposomes. Although TAT-PEG liposomes were efficiently internalized into cells, the efficacy of endosomal escape was insufficient. The transfection efficiencies of TAT-PEG liposomes were enhanced by about 30-fold when BLs and US exposure were used. We also confirmed that BLs and US exposure could not enhance the direct transportation of TAT-PEG liposomes into cells. Confocal microscopy showed that BLs and US exposure promoted endosomal escape of TAT-PEG liposomes. Our results suggested that BLs and US exposure could enhance transfection efficiency by promoting endosomal escape, which was independent of modified molecules of carriers. Thus, BLs and US exposure can be a useful tool to achieve efficient gene transfection by improving endosomal escape of various carriers.

Transcutaneous Ultrasound Augments Naked DNA Transfection of Skeletal Muscle

We have previously reported that the transfection efficiency of laminin-derived AG73-peptide labeled polyethyleneglycol-modified liposomes (AG73-PEG liposomes) was enhanced by echo-contrast gas entrapping PEG liposomes (Bubble liposomes, BLs) and ultrasound (US) exposure by improving endosomal escape. However, it has not been well understood whether BLs and US exposure can enhance the transfection efficiency of other carriers except AG73-PEG liposomes. In this study, to evaluate whether BLs and US exposure can be generally applied to gene delivery carriers, we focused on folate as a model ligand and examined whether BLs and US exposure could enhance the transfection efficiency of folate-PEG liposomes. Folate-PEG liposomes could internalize into cells efficiently, whereas they could not deliver genes into cytosol from endosomes sufficiently. BLs and US exposure could enhance the transfection efficiency of folate-PEG liposomes compared with folate-PEG liposomes alone without their direct induction into cells. These results suggested that BLs and US exposure could enhance the transfection efficiency of folate-PEG liposomes in the same manner as AG73-PEG liposomes. Thus, BLs and US exposure may be a promising tool to achieve efficient gene transfection into various gene carriers in general.

Recently, we reported the accelerated gene transfection efficiency of laminin-derived AG73-peptide-labeled polyethylene glycol-modified liposomes (AG73-PEG liposomes) and cell penetrating TAT-peptide labeled PEG liposomes using PEG-modified liposomes, which trap echo-contrast gas, "Bubble liposomes" (BLs), and ultrasound (US) exposure. BLs and US exposure were reported to enhance the endosomal escape of AG73-PEG liposomes, thereby leading to increased gene expression. However, the mechanism behind the effect of BLs and US exposure on endosomes is not well understood. US exposure was reported to induce an influx of calcium ions (Ca²⁺) by enhancing permeability of the cell membrane. Therefore, we examined the effect of Ca²⁺ on the endosomal escape and transfection efficiency of AG73-PEG liposomes, which were previously enhanced by BLs and US exposure. For cells treated with EGTA, the endosomal escape and gene expression of AG73-PEG liposomes were not enhanced by BLs and US exposure. Similarly, transfection efficiency of the AG73-PEG liposomes in ATP-depleted cells was not enhanced. Our results suggest that Ca²⁺ and ATP are necessary for the enhanced endosomal escape and gene expression of AG73-PEG liposomes by BLs and US exposure. These findings may contribute to the development of useful techniques to improve endosomal escape and achieve efficient gene transfection.

Objective To investigate the optimal ultrasound exposure parameter on H22 neoplasms of mice meditated by ultrasound exposure combined with self-made nanobubbles, and then observe their therapeutic effect combined with cisplatin and their possible mechanism of anti-tumor. Methods Thirty mice engrafts models with subcutaneous H22 neoplasms were established and divided into 6 groups randomly, which received ultrasound exposure at different intensity and exposure time. The contrast enhanced ultrasound imaging (CEUS ) was performed in every group at the four time points of before treatment and at 0 h, 24 h, 72 h after treatment. To obtain the optimal ultrasound parameters, the tumor inhibitory effect was assessed by enhanced intensity (EI) and microvascular density (MVD). The H22 tumor were treated by ultrasound exposure nanobubbles combined with cisplatin to observe their tumor growth inhibition rate, and the microvessels density and nuclear associated antigen Ki-67 proliferation index were measured by immunohistochemical staining. Results There was a statistically difference in enhanced intensity (EI) between the experimental groups and control group (P<0.05=. With the increasing of ultrasound intensity and exposure time, the tumor inhibitory effect was more obvious, with an increasing side reactions. Except the simple ultrasound group, there was a statistical difference in tumor inhibition, the mean MVD and the tumor cell proliferation index (KI-67) between control group and the other ultrasound therapy groups (P<0.05=. The tumor inhibitory rate was the highest (tumor inhibition rate 70.0%) and the mean MVD and KI-67 expression were the lowest (P<0.05= in the combination group comparing with the others. Conclusions The ideal ultrasound exposure parameter of tumor inhibition showed that exposure intensity chose 1 W/cm2 and exposure time chose 1 min or 3 min intermittence. The ultrasound exposure self-made nanobubbles combined with cisplatin could enhance the tumor inhibitory effect.Its mechanism may be related to the decrease of microvascular density, the inbition of tumor cell proliferation and the increase of tumor cell necrosis. Key words: Ultrasonography; Microbubbles; Liver neoplasms, experimental; Cisplatin

Skin, our first interface to the external environment, is subjected to oxidative stress caused by a variety of factors such as solar ultraviolet, infrared and visible light, environmental pollution, including ozone and particulate matters, and psychological stress. Excessive reactive species, including reactive oxygen species and reactive nitrogen species, exacerbate skin pigmentation and aging, which further lead to skin tone unevenness, pigmentary disorder, skin roughness and wrinkles. Besides these, skin microbiota are also a very important factor ensuring the proper functions of skin. While environmental factors such as UV and pollutants impact skin microbiota compositions, skin dysbiosis results in various skin conditions. In this review, we summarize the generation of oxidative stress from exogenous and endogenous sources. We further introduce current knowledge on the possible roles of oxidative stress in skin pigmentation and aging, specifically with emphasis on oxidative stress and skin pigmentation. Meanwhile, we summarize the science and rationale of using three well-known antioxidants, namely vitamin C, resveratrol and ferulic acid, in the treatment of hyperpigmentation. Finally, we discuss the strategy for preventing oxidative stress-induced skin pigmentation and aging.

Ultrasound (US) exposures are widely used with in vitro cell systems e.g. in stem cell and tissue engineering research. However, without the knowledge of factors affecting the level of US exposure, the outcome of the biological result may vary from test to test or even be misinterpreted. Thereby, some of the factors affecting in vitro US exposures were studied.The level of US exposure was characterized in standard commercial cell culturing plates. The temperature distributions were measured inside the wells using infrared camera and fine wire thermocouples, and pressure and intensity distributions using a laser vibrometer and a schlieren system. The measurements were made at operating frequency of around 1 MHz with varying temporal parameters and powers (up to 2 W of acoustic power).Heat accumulation between the wells varied up to 40–50% depending on the location of the well on the plate. This well‐to‐well variation was be linked to the activity of reporter plasmid on osteoblastic cells. Similar temperature variations within the wells were also measured. Small sub‐wavelength change in the exposure distance or, respectively, liquid volume inside the well was found to alter the acoustic field in both magnitude and shape due the standing waves.The gathered data reveals the complexity of the acoustic field in a typical in vitro set‐up and gives new information about the environment of the in vitro cells during US exposures. This data may be especially useful when US set‐ups are designed or characterized.

Sono-respond on thermosensitive polymer microgels based on cross-linked poly(N-isopropylacrylamide-co-acrylic acid)

Event Abstract Back to Event Engineering an ultrasound activated implant that provides on demand BMP-2 release for bone regeneration Gazelle Crasto1, Norbert Kartner2, Cameron Clokie1, Morris F. Manolson2, 3 and Sean A. Peel1, 4 1 University of Toronto, Oral and Maxillofacial Surgery, Canada 2 University of Toronto, Dental Research Institute, Canada 3 University of Toronto, Department of Biochemistry, Canada 4 Induce Biologics Inc, Canada Introduction: Recombinant bone morphogenetic protein 2 (BMP) implants can be an effective alternative to autogenous bone grafts. These advantages are offset, however, by cost and safety concerns due to the high initial dose of BMP required to compensate for its rapid release from the implant. To address this, we developed a novel protein delivery system, where liposomes sequester BMP at the bone defect site, until it is released by application of clinical ultrasound (US). Materials and Methods: We screened and characterized physical, chemical and ultrasound release properties of nine different liposome formulations. In vitro, release of BMP from liposomes was assessed following US exposure by varying exposure, pressure and frequency of US. Bone induction by the BMP-liposomes was evaluated in vivo in a mouse muscle pouch model. 16 groups of 10 mice each were implanted with BMP-containing liposomes and subjected to different US exposure profiles: single US treatment on day 0, 7 or 14 or dual exposure to US on day 0 and 7, or day 7 and 14, or twice on day 0, day 7 or day 14. The mice were harvested 28 days post last US treatment and micro CT and histology were used to quantitatively and qualitatively measure newly induced bone. Results: In vitro, Increase in pressure, frequency and time resulted in increased release of bioactive BMP-2 from liposomes. In vivo, animal studies revealed only US triggered release of BMP-2 from liposomes induced bone formation. Most importantly no bone formation was detected in mice containing BMP-liposomes that did not receive US. Enhanced bone formation was observed in groups where implants received two US treatments (Fig. 2) on day 0 and 7 instead of a single treatment (Fig. 1) on day 0, 7 or 14 or two treatments on the same day . The study further demonstrates BMP-liposomes can be used to control deliver BMP, additionally multiple early timed release of BMP results in enhanced bone formation. Conclusions: We have developed an implant that induces bone formation on US triggered controlled release of BMP-2 from liposomes. Additionally multiple rounds of US exposure increased bone formation compared to single exposure. G.J.C. was supported by NSERC Ph.D. Scholarship, Canadian Arthritis Network- The Arthritis Society Ph.D. Scholarship, Gerald Baker Oral Surgery Scholarship, Faculty of Dentistry- Harron Scholarship, Ontario Graduate Student-Science and Technology Scholarship.; Funding was provided by Dental Faculty Research Grant (DFRG).; Materials were provided by Induce Biologics Inc. Keywords: Bone Regeneration, growth factor, nanoparticle, delivery Conference: 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016. Presentation Type: Poster Topic: Regenerative medicine: biomaterials for control of tissue induction Citation: Crasto G, Kartner N, Clokie C, Manolson MF and Peel SA (2016). Engineering an ultrasound activated implant that provides on demand BMP-2 release for bone regeneration. Front. Bioeng. Biotechnol. Conference Abstract: 10th World Biomaterials Congress. doi: 10.3389/conf.FBIOE.2016.01.02878 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 27 Mar 2016; Published Online: 30 Mar 2016. Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Gazelle Crasto Norbert Kartner Cameron Clokie Morris F Manolson Sean A Peel Google Gazelle Crasto Norbert Kartner Cameron Clokie Morris F Manolson Sean A Peel Google Scholar Gazelle Crasto Norbert Kartner Cameron Clokie Morris F Manolson Sean A Peel PubMed Gazelle Crasto Norbert Kartner Cameron Clokie Morris F Manolson Sean A Peel Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Ultrasound Reverses Multidrug Resistance in Human Cancer Cells by Altering Gene Expression of ABC Transporter Proteins and Bax Protein

Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter Facebook Reddit LinkedIn Tools Icon Tools Reprints and Permissions Cite Icon Cite Search Site Citation Daiki Omata, Yoichi Negishi, Yoko Endo‐Takahashi, Ryo Suzuki, Kazuo Maruyama, Motoyoshi Nomizu, Yukihiko Aramaki; Ultrasound‐targeted Bubble Liposome Destruction Enhances AG73‐mediated Gene Transfer by Improvement of Intracellular Trafficking. AIP Conf. Proc. 12 September 2011; 1359 (1): 326–329. https://doi.org/10.1063/1.3607927 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAIP Publishing PortfolioAIP Conference Proceedings Search Advanced Search |Citation Search

Au/TiO2 nanocomposite as a triple-sensitizer for 808 and 650 nm phototherapy and sonotherapy: Synergistic therapy of melanoma cancer in vitro

A novel strategy utilizing ultrasound for antigen delivery in dendritic cell-based cancer immunotherapy

Sonodynamic therapy has received increasing attention for cancer treatments as an alternative to photodynamic therapy. However, its clinical applications have been limited by the lack of a sonosensitizer that is capable of producing sufficient amounts of reactive oxygen species (ROS) in response to ultrasound (US) exposure. Herein, PEGylated mesoporous silica-titania nanoparticles (P-MSTNs) are prepared and used as US-responsive nanocarriers for cancer sonotheranostics. Perfluorohexane (PFH), which is chosen as the gas precursor, is physically encapsulated into P-MSTNs using the oil-in-water emulsion method. Owing to the vaporization of the gas precursor, PFH@P-MSTNs (137 nm in diameter) exhibit a strong photoacoustic signal in vivo for at least 6 h. Compared to P-MSTNs, PFH@P-MSTNs generate significantly higher amounts of ROS due to the nanobubble-induced cavitation in the presence of US. When systemically administered to tumor-bearing mice, PFH@P-MSTNs effectively accumulate in the tumor site due to the passive targeting mechanism. Consequently, PFH@P-MSTNs show much higher antitumor efficacy than P-MSTNs due to the enhanced cavitation-mediated ROS generation in response to US exposure. It is considered that PFH@P-MSTNs may hold significant potential for cancer sonotheranostics.