For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
8
views
24
references
 Top references
cited by
15
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      176
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Cryo-EM Visualization of Lipid and Polymer-Stabilized Perfluorocarbon Gas Nanobubbles - A Step Towards Nanobubble Mediated Drug Delivery

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Gas microbubbles stabilized with lipids, surfactants, proteins and/or polymers are widely used clinically as ultrasound contrast agents. Because of their large 1–10 µm size, applications of microbubbles are confined to the blood vessels. Accordingly, there is much interest in generating nanoscale echogenic bubbles (nanobubbles), which can enable new uses of ultrasound contrast agents in molecular imaging and drug delivery, particularly for cancer applications. While the interactions of microbubbles with ultrasound have been widely investigated, little is known about the activity of nanobubbles under ultrasound exposure. In this work, we demonstrate that cryo-electron microscopy (cryo-EM) can be used to image nanoscale lipid and polymer-stabilized perfluorocarbon gas bubbles before and after their destruction with high intensity ultrasound. In addition, cryo-EM can be used to observe electron-beam induced dissipation of nanobubble encapsulated perfluorocarbon gas.

          Related collections

          Most cited references24

          • Record: found
          • Abstract: found
          • Article: found
          Is Open Access

          Cryo-EM enters a new era

          Werner Kühlbrandt (2014)
          Advances in detector hardware and image-processing software have led to a revolution in the use of electron cryo-microscopy to determine complex molecular structures at high resolution.
          Article 0 comments Cited 86 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Ultrasound contrast microbubbles in imaging and therapy: physical principles and engineering.

            S Qin, K Ferrara, C Caskey (2009)
            Microbubble contrast agents and the associated imaging systems have developed over the past 25 years, originating with manually-agitated fluids introduced for intra-coronary injection. Over this period, stabilizing shells and low diffusivity gas materials have been incorporated in microbubbles, extending stability in vitro and in vivo. Simultaneously, the interaction of these small gas bubbles with ultrasonic waves has been extensively studied, resulting in models for oscillation and increasingly sophisticated imaging strategies. Early studies recognized that echoes from microbubbles contained frequencies that are multiples of the microbubble resonance frequency. Although individual microbubble contrast agents cannot be resolved-given that their diameter is on the order of microns-nonlinear echoes from these agents are used to map regions of perfused tissue and to estimate the local microvascular flow rate. Such strategies overcome a fundamental limitation of previous ultrasound blood flow strategies; the previous Doppler-based strategies are insensitive to capillary flow. Further, the insonation of resonant bubbles results in interesting physical phenomena that have been widely studied for use in drug and gene delivery. Ultrasound pressure can enhance gas diffusion, rapidly fragment the agent into a set of smaller bubbles or displace the microbubble to a blood vessel wall. Insonation of a microbubble can also produce liquid jets and local shear stress that alter biological membranes and facilitate transport. In this review, we focus on the physical aspects of these agents, exploring microbubble imaging modes, models for microbubble oscillation and the interaction of the microbubble with the endothelium.
            Article 0 comments Cited 82 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found
              Is Open Access

              Design and evaluation of doxorubicin-containing microbubbles for ultrasound-triggered doxorubicin delivery: cytotoxicity and mechanisms involved.

              Ine Lentacker, Bart Geers, Joseph Demeester … (2010)
              Drug delivery with microbubbles and ultrasound is gaining more and more attention in the drug delivery field due to its noninvasiveness, local applicability, and proven safety in ultrasonic imaging techniques. In this article, we tried to improve the cytotoxicity of doxorubicin (DOX)-containing liposomes by preparing DOX-liposome-containing microbubbles for drug delivery with therapeutic ultrasound. In this way, the DOX release and uptake can be restricted to ultrasound-treated areas. Compared to DOX-liposomes, DOX-loaded microbubbles killed at least two times more melanoma cells after exposure to ultrasound. After treatment of the melanoma cells with DOX-liposome-loaded microbubbles and ultrasound, DOX was mainly present in the nuclei of the cancer cells, whereas it was mainly detected in the cytoplasm of cells treated with DOX-liposomes. Exposure of cells to DOX-liposome-loaded microbubbles and ultrasound caused an almost instantaneous cellular entry of the DOX. At least two mechanisms were identified that explain the fast uptake of DOX and the superior cell killing of DOX-liposome-loaded microbubbles and ultrasound. First, exposure of DOX-liposome-loaded microbubbles to ultrasound results in the release of free DOX that is more cytotoxic than DOX-liposomes. Second, the cellular entry of the released DOX is facilitated due to sonoporation of the cell membranes. The in vitro results shown in this article indicate that DOX-liposome-loaded microbubbles could be a very interesting tool to obtain an efficient ultrasound-controlled DOX delivery in vivo.
              Article 0 comments Cited 70 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Contributors
                Phoebe L. Stewart: pls47@case.edu
                Agata A. Exner:
                ORCID: http://orcid.org/0000-0003-3913-7066
                agata.exner@case.edu
                Journal
                Journal ID (nlm-ta): Sci Rep
                Journal ID (iso-abbrev): Sci Rep
                Title: Scientific Reports
                Publisher: Nature Publishing Group UK (London )
                ISSN (Electronic): 2045-2322
                Publication date (Electronic): 18 October 2017
                Publication date PMC-release: 18 October 2017
                Publication date Collection: 2017
                Volume: 7
                Electronic Location Identifier: 13517
                Affiliations
                [1 ]ISNI 0000 0001 2164 3847, GRID grid.67105.35, Department of Biomedical Engineering, , Case Western Reserve University, Cleveland, ; Ohio, USA
                [2 ]ISNI 0000 0001 2164 3847, GRID grid.67105.35, Department of Pharmacology, , Case Western Reserve University, Cleveland, ; Ohio, USA
                [3 ]ISNI 0000 0001 2164 3847, GRID grid.67105.35, Cleveland Center for Membrane and Structural Biology, Case Western Reserve University, Cleveland, ; Ohio, USA
                [4 ]ISNI 0000 0001 2164 3847, GRID grid.67105.35, Department of Radiology, , Case Western Reserve University, Cleveland, ; Ohio, USA
                Author information
                http://orcid.org/0000-0003-0380-7136
                http://orcid.org/0000-0002-8255-479X
                http://orcid.org/0000-0003-3913-7066
                Article
                Publisher ID: 13741
                DOI: 10.1038/s41598-017-13741-1
                PMC ID: 5647366
                PubMed ID: 29044154
                SO-VID: e8e68a44-af8b-4847-a074-4ba0034b7235
                Copyright © © The Author(s) 2017
                License:

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                Date received : 28 July 2017
                Date accepted : 27 September 2017
                Categories
                Subject: Article
                Custom metadata
                issue-copyright-statement © The Author(s) 2017

                ScienceOpen disciplines: Uncategorized
                Data availability:
                ScienceOpen disciplines: Uncategorized

                Comments

                Comment on this article

                scite_

                Similar content176

                See all similar

                Cited by15

                See all cited by

                Most referenced authors342

                See all reference authors