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Published VersionCC BY V4.0, Open Access
Journal article
Stably engineered nanobubbles and ultrasound - An effective platform for enhanced macromolecular delivery to representative cells of the retina
PLoS One, Vol.12(5), pp.1-17
2017
PMID: 28542473
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.
Details
- Title
- Stably engineered nanobubbles and ultrasound - An effective platform for enhanced macromolecular delivery to representative cells of the retina
- Authors
- Sachin S. Thakur - The University of QueenslandMicheal S Ward - The University of QueenslandAmirali Popat - Translational Research InstituteNicole B Flemming - Translational Research InstituteMarie-Odile Parat - The University of QueenslandNigel L. Barnett - Queensland Eye InstituteHarendra S. Parekh (Corresponding Author) - The University of Queensland
- Publication details
- PLoS One, Vol.12(5), pp.1-17
- Publisher
- Public Library of Science
- Date published
- 2017
- DOI
- 10.1371/journal.pone.0178305
- ISSN
- 1932-6203
- PMID
- 28542473
- Copyright note
- © 2017 Thakur et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
- Data Availability
- All relevant data are within the paper and its Supporting Information files.
- Grant note
- This work was supported by the National Health and Medical Research Council of Australia (Grant number: 1023444); the Juvenile Diabetes Research Foundation International (Grant number: 3-2013-217); and the University of Queensland School of Pharmacy Research and Maintenance Funds.
- Organisation Unit
- School of Health - Biomedicine
- Language
- English
- Record Identifier
- 991167745902621
- Output Type
- Journal article
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