Stably engineered nanobubbles and ultrasound - An effective platform for enhanced macromolecular delivery to representative cells of the retina

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dc.contributor.author Thakur, Sachin en
dc.contributor.author Ward, MS en
dc.contributor.author Popat, A en
dc.contributor.author Flemming, NB en
dc.contributor.author Parat, MO en
dc.contributor.author Barnett, NL en
dc.contributor.author Parekh, HS en
dc.date.accessioned 2017-10-01T20:55:20Z en
dc.date.issued 2017-05-25 en
dc.identifier.citation PLoS ONE 12(5):17 pages Article number e0178305 25 May 2017 en
dc.identifier.issn 1932-6203 en
dc.identifier.uri http://hdl.handle.net/2292/35818 en
dc.description.abstract Herein we showcase the potential of ultrasound-responsive nanobubbles in enhancing macromolecular permeation through layers of the retina, ultimately leading to significant and direct intracellular delivery; this being effectively demonstrated across three relevant and distinct retinal cell lines. Stably engineered nanobubbles of a highly homogenous and echogenic nature were fully characterised using dynamic light scattering, B-scan ultrasound and transmission electron microscopy (TEM). The nanobubbles appeared as spherical liposome-like structures under TEM, accompanied by an opaque luminal core and darkened corona around their periphery, with both features indicative of efficient gas entrapment and adsorption, respectively. A nanobubble +/- ultrasound sweeping study was conducted next, which determined the maximum tolerated dose for each cell line. Detection of underlying cellular stress was verified using the biomarker heat shock protein 70, measured before and after treatment with optimised ultrasound. Next, with safety to nanobubbles and optimised ultrasound demonstrated, each human or mouse-derived cell population was incubated with biotinylated rabbit-IgG in the presence and absence of ultrasound +/- nanobubbles. Intracellular delivery of antibody in each cell type was then quantified using Cy3-streptavidin. Nanobubbles and optimised ultrasound were found to be negligibly toxic across all cell lines tested. Macromolecular internalisation was achieved to significant, yet varying degrees in all three cell lines. The results of this study pave the way towards better understanding mechanisms underlying cellular responsiveness to ultrasound-triggered drug delivery in future ex vivo and in vivo models of the posterior eye. en
dc.publisher Public Library of Science (PLoS) en
dc.relation.ispartofseries PLoS ONE en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from http://www.sherpa.ac.uk/romeo/issn/1932-6203/ en
dc.rights.uri https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm en
dc.rights.uri https://creativecommons.org/licenses/by/4.0/ en
dc.title Stably engineered nanobubbles and ultrasound - An effective platform for enhanced macromolecular delivery to representative cells of the retina en
dc.type Journal Article en
dc.identifier.doi 10.1371/journal.pone.0178305 en
pubs.issue 5 en
pubs.volume 12 en
dc.description.version VoR - Version of Record en
dc.rights.holder Copyright: The author en
dc.identifier.pmid 28542473 en
dc.rights.accessrights http://purl.org/eprint/accessRights/OpenAccess en
pubs.subtype Article en
pubs.elements-id 627454 en
pubs.org-id Medical and Health Sciences en
pubs.org-id Pharmacy en
pubs.number e0178305 en
pubs.record-created-at-source-date 2017-05-29 en
pubs.dimensions-id 28542473 en


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https://creativecommons.org/licenses/by/4.0/ Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by/4.0/

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