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      International Journal of Nanomedicine (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the application of nanotechnology in diagnostics, therapeutics, and drug delivery systems throughout the biomedical field. Sign up for email alerts here.

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      Is Open Access

      Photothermal treatment of liver cancer with albumin-conjugated gold nanoparticles initiates Golgi Apparatus–ER dysfunction and caspase-3 apoptotic pathway activation by selective targeting of Gp60 receptor

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          Abstract

          We present a method of enhanced laser thermal ablation of HepG2 cells based on a simple gold nanoparticle (GNP) carrier system such as serum albumin (Alb), and demonstrate its selective therapeutic efficacy compared with normal hepatocyte cells. HepG2 or hepatocytes were treated with Alb-GNPs at various concentrations and various incubation times, and further irradiated using a 2 W, 808 nm laser. Darkfield microscopy and immunochemical staining was used to demonstrate the selective internalization of Alb-GNPs inside the HepG2 cells via Gp60 receptors targeting. The postirradiation apoptotic rate of HepG2 cells treated with Alb-GNPs ranged from 25.8% (for 5 μg/mL) to 48.2% (for 50 μg/mL) at 60 seconds, while at 30 minutes the necrotic rate increased from 35.7% (5 μg/mL) to 52.3% (50 μg/mL), P-value <0.001. Significantly lower necrotic rates were obtained when human hepatocytes were treated with Alb-GNPs in a similar manner. We also showed by means of immunocytochemistry that photothermal treatment of Alb-conjugated GNPs in liver cancer initiates Golgi apparatus–endoplasmic reticulum dysfunction with consequent caspase-3 apoptotic pathway activation and cellular apoptosis. The presented results may become a new method of treating cancer cells by selective therapeutic vectors using nanolocalized thermal ablation by laser heating.

          Most cited references29

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          Hypoxia signalling through mTOR and the unfolded protein response in cancer.

          Hypoxia occurs in the majority of tumours, promoting angiogenesis, metastasis and resistance to therapy. Responses to hypoxia are orchestrated in part through activation of the hypoxia-inducible factor family of transcription factors (HIFs). Recently, two additional O(2)-sensitive signalling pathways have also been implicated: signalling through the mammalian target of rapamycin (mTOR) kinase and signalling through activation of the unfolded protein response (UPR). Although they are activated independently, growing evidence suggests that HIF-, mTOR- and UPR-dependent responses to hypoxia act in an integrated way, influencing each other and common downstream pathways that affect gene expression, metabolism, cell survival, tumorigenesis and tumour growth.
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            Gold nanoparticles as novel agents for cancer therapy.

            Gold nanoparticles are emerging as promising agents for cancer therapy and are being investigated as drug carriers, photothermal agents, contrast agents and radiosensitisers. This review introduces the field of nanotechnology with a focus on recent gold nanoparticle research which has led to early-phase clinical trials. In particular, the pre-clinical evidence for gold nanoparticles as sensitisers with ionising radiation in vitro and in vivo at kilovoltage and megavoltage energies is discussed.
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              Size matters: gold nanoparticles in targeted cancer drug delivery.

              Cancer is the current leading cause of death worldwide, responsible for approximately one quarter of all deaths in the USA and UK. Nanotechnologies provide tremendous opportunities for multimodal, site-specific drug delivery to these disease sites and Au nanoparticles further offer a particularly unique set of physical, chemical and photonic properties with which to do so. This review will highlight some recent advances, by our laboratory and others, in the use of Au nanoparticles for systemic drug delivery to these malignancies and will also provide insights into their rational design, synthesis, physiological properties and clinical/preclinical applications, as well as strategies and challenges toward the clinical implementation of these constructs moving forward.
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                Author and article information

                Journal
                Int J Nanomedicine
                Int J Nanomedicine
                International Journal of Nanomedicine
                International Journal of Nanomedicine
                Dove Medical Press
                1176-9114
                1178-2013
                2015
                26 August 2015
                : 10
                : 5435-5445
                Affiliations
                [1 ]Nanomedicine Department, Regional Institute of Gastroenterology and Hepatology “Octavian Fodor”, University of Medicine and Pharmacy, “Iuliu Hatieganu”, Croitorilor, Cluj-Napoca, Romania
                [2 ]Department of Surgery, University of Medicine and Pharmacy, “Iuliu Hatieganu”, Croitorilor, Cluj-Napoca, Romania
                [3 ]Department of Pathology, Faculty of Veterinary Medicine, University of Agricultural Sciences and Veterinary Medicine, Croitorilor, Cluj-Napoca, Romania
                [4 ]Department of Gastroenterology, University of Medicine and Pharmacy, “Iuliu Hatieganu”, Croitorilor, Cluj-Napoca, Romania
                [5 ]Department of Physiology, University of Medicine and Pharmacy, “Iuliu Hatieganu”, Croitorilor, Cluj-Napoca, Romania
                Author notes
                Correspondence: Teodora Mocan; Cornel Iancu, Nanomedicine Department, Regional Institute of Gastroenterology and Hepatology ‘Octavian Fodor’, Croitorilor Street 19-21, Cluj Napoca, 400162, Romania, Tel +40 264 439 696, Fax +40 264 439 696, Email teodora.mocan@ 123456umfcluj.ro ; cornel.iancu@ 123456umfcluj.ro
                Article
                ijn-10-5435
                10.2147/IJN.S86495
                4554431
                26346915
                ce042428-e385-458d-a1fd-6d351ef3fa39
                © 2015 Mocan et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Original Research

                Molecular medicine
                liver cancer,gold nanoparticles,hepg2 cells,functionalization,laser irradiation,albumin

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