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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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      Oxygen and indocyanine green loaded phase-transition nanoparticle-mediated photo-sonodynamic cytotoxic effects on rheumatoid arthritis fibroblast-like synoviocytes

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          Abstract

          Background

          Photodynamic therapy and sonodynamic therapy are developing, minimally invasive, and site-specific modalities for cancer therapy. A combined strategy PSDT (photodynamic therapy followed by sonodynamic therapy) has been proposed in this study. Here, we aimed to develop novel biodegradable poly(DL-lactide- co-glycolic acid) phase-transition nanoparticles simultaneously loaded with oxygen and indocyanine green (OI-NPs) and to investigate the cytotoxic effects and the potential mechanisms of OI-NP–mediated PSDT on MH7A synoviocytes.

          Methods

          The OI-NPs were prepared using a modified double emulsion method and the physicochemical properties were determined. The cellular uptake of OI-NPs was detected by confocal microscopy and flow cytometry. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay, flow cytometry, and Hoechst 33342/propidium iodide double staining were used to determine the cytotoxic effect of OI-NP–mediated PSDT on MH7A cells. Fluorescence microscope and fluorescence microplate reader were used to detect reactive oxygen species (ROS) generation.

          Results

          The OI-NPs were a stable and efficient carrier to deliver oxygen and indocyanine green, and enhanced cellular uptake was observed in MH7A cells with the nanoparticles. OI-NP–mediated PSDT caused more serious cell damage and more evident cell apoptosis, compared with other groups. Furthermore, increased generation of intracellular ROS was detected in MH7A cells treated with PSDT. Interestingly, the OI-NP–mediated PSDT-induced cell viability loss was effectively rescued by pretreatment with the ROS scavenger N-acetylcysteine.

          Conclusion

          Multifunctional OI-NPs were successfully developed and characterized for the combined delivery of oxygen and indocyanine green, and OI-NP–mediated PSDT would be a potential cytotoxic treatment for MH7A cells. This study may provide a novel strategy for the treatment of RA and develop a model of theranostic application through phase-transition nanoparticle-mediated PSDT in the future.

          Most cited references38

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          Fibroblast-like synoviocytes: key effector cells in rheumatoid arthritis.

          Rheumatoid arthritis (RA) remains a significant unmet medical need despite significant therapeutic advances. The pathogenesis of RA is complex and includes many cell types, including T cells, B cells, and macrophages. Fibroblast-like synoviocytes (FLS) in the synovial intimal lining also play a key role by producing cytokines that perpetuate inflammation and proteases that contribute to cartilage destruction. Rheumatoid FLS develop a unique aggressive phenotype that increases invasiveness into the extracellular matrix and further exacerbates joint damage. Recent advances in understanding the biology of FLS, including their regulation regulate innate immune responses and activation of intracellular signaling mechanisms that control their behavior, provide novel insights into disease mechanisms. New agents that target FLS could potentially complement the current therapies without major deleterious effect on adaptive immune responses.
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            Light-absorbing properties, stability, and spectral stabilization of indocyanine green.

            The absorption spectrum of indocyanine green depends on the nature of the solvent medium and on the dye concentration. Binding to plasma proteins causes the principal peaks in the absorption spectrum to shift about 25 nm toward the higher wavelengths. The much greater influence on the spectrum of the dye concentration results from progressive aggregate formation with increasing concentration. Indocyanine green solutions therefore do not follow Lambert-Beer's law above 15 mg-I-1 (in plasma). Indocyanine green solutions in plasma and concentrated (1,000 mg-I-1) solutions in distilled water are stable for at least 4 h. In long-term experiments the optical density of indocyanine green solutions in plasma as well as in distilled water generally diminishes, even in the dark. On the 7th day a new absorption maximum starts to appear at gamma=900 nm, possibly caused by further aggregate formation leading to much larger particles. Spectral stabilization after injection of a concentrated solution into the blood is most rapid when the dye is dissolved in distilled water. Spectral stabilization slows down with decreasing temperature. As rapid spectral stabilization is essential in quantitative dye dilution studies, the practice of adding a albumin and/or isotonic saline solution to the injectate should be discontinued. When a 10 g-1(-1) aqueous solution of indocyanine green is used, spectral stabilization takes less than 1.5 a (at 37 degrees C), which is sufficiently fast for almost any application.
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              Fluorescence properties and metabolic features of indocyanine green (ICG) as related to angiography.

              Indocyanine green (ICG) is a fluorescent dye that has been used for the imaging of retinal and choroidal vasculatures for more than 30 years. Its high molecular weight, specific metabolic features, and its infrared spectra make the specificity of the images obtained with this dye in ophthalmology. The focus of this paper is to review the basic properties of ICG and to show how some clinical features related to basic properties also depend on the instrumentation used to perform ICG angiography. Indocyanine green has a complex molecular structure that leads to amphiphilic properties, that is, both hydrophilic and lipophilic properties. These properties explain that a specific interaction with phospholipids influences the emission spectrum and the fluorescence yield of ICG. The composition of cell membranes mainly composed of phospholipid bilayers is consistent with a binding and/or a diffusion of ICG molecules observed on angiograms. Likewise, ICG can bind to the lipid component of miliary drusen, explaining their hyperfluorescence. A knowledge of ICG basic properties and interactions may allow a better understanding of angiograms performed with this dye.
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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
                2017
                09 January 2017
                : 12
                : 381-393
                Affiliations
                [1 ]Department of Pharmacy, First Affiliated Hospital of Chongqing Medical University
                [2 ]Department of Ultrasound, Institute of Ultrasound Imaging, Second Affiliated Hospital of Chongqing Medical University
                [3 ]State Key Laboratory of Ultrasound Engineering in Medicine Co-founded by Chongqing and the Ministry of Science and Technology
                [4 ]Department of Obstetrics and Gynecology, Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China
                Author notes
                Correspondence: Shenyin Zhu; Shufang Chang, Department of Pharmacy, First Affiliated Hospital of Chongqing Medical University, No 1, Yixueyuan Road, Yuzhong District, Chongqing 400016, People’s Republic of China, Tel +86 23 8901 2401, Fax +86 23 6881 1793, Email zhushenyin0486@ 123456sina.com ; shfch2005@ 123456163.com
                Article
                ijn-12-381
                10.2147/IJN.S120902
                5234560
                28123298
                55f4604a-6326-4892-95aa-dbe04b019cd7
                © 2017 Tang et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. 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
                multifunctional nanoparticles,indocyanine green,synoviocytes,reactive oxygen species,apoptosis

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