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      Controlled gene and drug release from a liposomal delivery platform triggered by X-ray radiation

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          Abstract

          Liposomes have been well established as an effective drug delivery system, due to simplicity of their preparation and unique characteristics. However conventional liposomes are unsuitable for the on-demand content release, which limits their therapeutic utility. Here we report X-ray-triggerable liposomes incorporating gold nanoparticles and photosensitizer verteporfin. The 6 MeV X-ray radiation induces verteporfin to produce singlet oxygen, which destabilises the liposomal membrane and causes the release of cargos from the liposomal cavity. This triggering strategy is demonstrated by the efficiency of gene silencing in vitro and increased effectiveness of chemotherapy in vivo. Our work indicates the feasibility of a combinatorial treatment and possible synergistic effects in the course of standard radiotherapy combined with chemotherapy delivered via X-ray-triggered liposomes. Importantly, our X-ray-mediated liposome release strategy offers prospects for deep tissue photodynamic therapy, by removing its depth limitation.

          Abstract

          X-ray radiation has excellent tissue penetration depth, making it a useful trigger for deep tissue cancer therapy. Here, the authors design X-ray triggered drug/gene-loaded liposomes by embedding photosensitizers and gold nanoparticles in the liposome bilayer, and demonstrate their efficacy in cancer and gene therapy.

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          Most cited references56

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          Progress and problems with the use of viral vectors for gene therapy.

          Gene therapy has a history of controversy. Encouraging results are starting to emerge from the clinic, but questions are still being asked about the safety of this new molecular medicine. With the development of a leukaemia-like syndrome in two of the small number of patients that have been cured of a disease by gene therapy, it is timely to contemplate how far this technology has come, and how far it still has to go.
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            Genetic and pharmacological disruption of the TEAD-YAP complex suppresses the oncogenic activity of YAP.

            The Drosophila TEAD ortholog Scalloped is required for Yki-mediated overgrowth but is largely dispensable for normal tissue growth, suggesting that its mammalian counterpart may be exploited for selective inhibition of oncogenic growth driven by YAP hyperactivation. Here we test this hypothesis genetically and pharmacologically. We show that a dominant-negative TEAD molecule does not perturb normal liver growth but potently suppresses hepatomegaly/tumorigenesis resulting from YAP overexpression or Neurofibromin 2 (NF2)/Merlin inactivation. We further identify verteporfin as a small molecule that inhibits TEAD-YAP association and YAP-induced liver overgrowth. These findings provide proof of principle that inhibiting TEAD-YAP interactions is a pharmacologically viable strategy against the YAP oncoprotein.
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              New Developments in Liposomal Drug Delivery.

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                Author and article information

                Contributors
                wei.deng@unsw.edu.au
                e.goldys@unsw.edu.au
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                13 July 2018
                13 July 2018
                2018
                : 9
                : 2713
                Affiliations
                [1 ]ISNI 0000 0001 2158 5405, GRID grid.1004.5, ARC Centre of Excellence for Nanoscale Biophotonics, Faculty of Science and Engineering, , Macquarie University, ; North Ryde, 2109 New South Wales Australia
                [2 ]ISNI 0000 0001 2158 5405, GRID grid.1004.5, Faculty of Medicine and Health Sciences, , Macquarie University, ; North Ryde, 2109 NSW Australia
                [3 ]ISNI 0000 0001 2288 8774, GRID grid.448878.f, Sechenov University, ; Moscow, 119992 Russia
                [4 ]ISNI 0000 0004 1936 834X, GRID grid.1013.3, Sydney Medical School, , University of Sydney, ; Sydney, 2050 NSW Australia
                [5 ]ISNI 0000 0004 0587 9093, GRID grid.412703.3, Department of Colorectal Surgery, , Royal North Shore Hospital, ; St Leonards, 2065 NSW Australia
                [6 ]ISNI 0000 0004 0466 4031, GRID grid.482157.d, Sydney Vital Translational Cancer Research, , Kolling Institute of Medical Research, Northern Sydney Local Health District, ; St Leonards, 2065 NSW Australia
                [7 ]ISNI 0000 0004 4902 0432, GRID grid.1005.4, Present Address: The Graduate School of Biomedical Engineering, , University of New South Wales, Sydney, ; Kensington, 2052 NSW Australia
                Author information
                http://orcid.org/0000-0002-8866-9838
                Article
                5118
                10.1038/s41467-018-05118-3
                6045614
                30006596
                d5759bfb-fe03-4ad6-adb9-623f2bfc139e
                © The Author(s) 2018

                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
                : 18 November 2016
                : 24 May 2018
                Funding
                Funded by: This work is supported by Discovery Early Career Researcher Award scheme (DE130100894) and Centre of Excellence scheme (CE140100003) from Australian Research Council.
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