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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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      ROS-Mediated Apoptosis and Autophagy in Ovarian Cancer Cells Treated with Peanut-Shaped Gold Nanoparticles

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          Abstract

          Background

          Even with considerable improvement in treatment of epithelial ovarian cancer achieved in recent years, an increasing chemotherapy resistance and disease 5-year relapse is recorded for a majority part of patients that encourages the search for better therapeutic options. Gold nanoparticles (Au NPs) due to plethora of unique physiochemical features are thoroughly tested as drug delivery, radiosensitizers, as well as photothermal and photodynamic therapy agents. Importantly, due to highly controlled synthesis, it is possible to obtain nanomaterials with directed size and shape.

          Methods

          In this work, we developed novel elongated-type gold nanoparticles in the shape of nanopeanuts (AuP NPs) and investigated their cytotoxic potential against ovarian cancer cells SKOV-3 using colorimetric and fluorimetric methods, Western blot, flow cytometry, and fluorescence microscopy.

          Results

          Peanut-shaped gold nanoparticles showed high anti-cancer activity in vitro against SKOV-3 cells at doses of 1–5 ng/mL upon 72 hours treatment. We demonstrate that AuP NPs decrease the viability and proliferation capability of ovarian cancer cells by triggering cell apoptosis and autophagy, as evidenced by flow cytometry and Western blot analyses. The overproduction of reactive oxygen species (ROS) was noted to be a critical mediator of AuP NPs-mediated cell death.

          Conclusion

          These data indicate that gold nanopeanuts might be developed as nanotherapeutics against ovarian cancer.

          Most cited references72

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          Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4

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            Apoptosis: a review of programmed cell death.

            The process of programmed cell death, or apoptosis, is generally characterized by distinct morphological characteristics and energy-dependent biochemical mechanisms. Apoptosis is considered a vital component of various processes including normal cell turnover, proper development and functioning of the immune system, hormone-dependent atrophy, embryonic development and chemical-induced cell death. Inappropriate apoptosis (either too little or too much) is a factor in many human conditions including neurodegenerative diseases, ischemic damage, autoimmune disorders and many types of cancer. The ability to modulate the life or death of a cell is recognized for its immense therapeutic potential. Therefore, research continues to focus on the elucidation and analysis of the cell cycle machinery and signaling pathways that control cell cycle arrest and apoptosis. To that end, the field of apoptosis research has been moving forward at an alarmingly rapid rate. Although many of the key apoptotic proteins have been identified, the molecular mechanisms of action or inaction of these proteins remain to be elucidated. The goal of this review is to provide a general overview of current knowledge on the process of apoptosis including morphology, biochemistry, the role of apoptosis in health and disease, detection methods, as well as a discussion of potential alternative forms of apoptosis.
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              Calculated absorption and scattering properties of gold nanoparticles of different size, shape, and composition: applications in biological imaging and biomedicine.

              The selection of nanoparticles for achieving efficient contrast for biological and cell imaging applications, as well as for photothermal therapeutic applications, is based on the optical properties of the nanoparticles. We use Mie theory and discrete dipole approximation method to calculate absorption and scattering efficiencies and optical resonance wavelengths for three commonly used classes of nanoparticles: gold nanospheres, silica-gold nanoshells, and gold nanorods. The calculated spectra clearly reflect the well-known dependence of nanoparticle optical properties viz. the resonance wavelength, the extinction cross-section, and the ratio of scattering to absorption, on the nanoparticle dimensions. A systematic quantitative study of the various trends is presented. By increasing the size of gold nanospheres from 20 to 80 nm, the magnitude of extinction as well as the relative contribution of scattering to the extinction rapidly increases. Gold nanospheres in the size range commonly employed ( approximately 40 nm) show an absorption cross-section 5 orders higher than conventional absorbing dyes, while the magnitude of light scattering by 80-nm gold nanospheres is 5 orders higher than the light emission from strongly fluorescing dyes. The variation in the plasmon wavelength maximum of nanospheres, i.e., from approximately 520 to 550 nm, is however too limited to be useful for in vivo applications. Gold nanoshells are found to have optical cross-sections comparable to and even higher than the nanospheres. Additionally, their optical resonances lie favorably in the near-infrared region. The resonance wavelength can be rapidly increased by either increasing the total nanoshell size or increasing the ratio of the core-to-shell radius. The total extinction of nanoshells shows a linear dependence on their total size, however, it is independent of the core/shell radius ratio. The relative scattering contribution to the extinction can be rapidly increased by increasing the nanoshell size or decreasing the ratio of the core/shell radius. Gold nanorods show optical cross-sections comparable to nanospheres and nanoshells, however, at much smaller effective size. Their optical resonance can be linearly tuned across the near-infrared region by changing either the effective size or the aspect ratio of the nanorods. The total extinction as well as the relative scattering contribution increases rapidly with the effective size, however, they are independent of the aspect ratio. To compare the effectiveness of nanoparticles of different sizes for real biomedical applications, size-normalized optical cross-sections or per micron coefficients are calculated. Gold nanorods show per micron absorption and scattering coefficients that are an order of magnitude higher than those for nanoshells and nanospheres. While nanorods with a higher aspect ratio along with a smaller effective radius are the best photoabsorbing nanoparticles, the highest scattering contrast for imaging applications is obtained from nanorods of high aspect ratio with a larger effective radius.
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                Author and article information

                Journal
                Int J Nanomedicine
                Int J Nanomedicine
                ijn
                intjnano
                International Journal of Nanomedicine
                Dove
                1176-9114
                1178-2013
                09 March 2021
                2021
                : 16
                : 1993-2011
                Affiliations
                [1 ]Department of Medical Microbiology and Nanobiomedical Engineering, Medical University of Bialystok , Bialystok, 15-222, Poland
                [2 ]Department of Medicinal Chemistry, Medical University of Bialystok , Bialystok, 15-222, Poland
                [3 ]Institute of Nuclear Physics Polish Academy of Sciences , Krakow, PL-31342, Poland
                [4 ]Department of Biopharmacy, Medical University of Bialystok , Bialystok, 15-222, Poland
                [5 ] Institute of Medical Sciences, Collegium Medicum, Jan Kochanowski University , Kielce, 25-317, Poland
                [6 ]Holy Cross Cancer Center in Kielce , Kielce, 25-734, Poland
                Author notes
                Correspondence: Robert Bucki Department of Medical Microbiology and Nanobiomedical Engineering, Medical University of Bialystok , Mickiewicza 2C, Bialystok, 15-222, PolandTel + 48 85 748 5793 Email buckirobert@gmail.com
                Author information
                http://orcid.org/0000-0002-4531-7277
                http://orcid.org/0000-0002-7934-6973
                http://orcid.org/0000-0001-6666-9688
                http://orcid.org/0000-0003-0168-1701
                http://orcid.org/0000-0003-4450-5011
                http://orcid.org/0000-0001-5901-400X
                http://orcid.org/0000-0001-7664-9226
                Article
                277014
                10.2147/IJN.S277014
                7955786
                33727811
                f0c75867-f212-42ae-8171-61587d2c358b
                © 2021 Piktel 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. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 19 August 2020
                : 08 December 2020
                Page count
                Figures: 7, References: 72, Pages: 19
                Funding
                Funded by: the National Science Centre, Poland;
                Funded by: Medical University of Bialystok, open-funder-registry 10.13039/501100005297;
                This work was financially supported by grants from the National Science Centre, Poland (UMO-2018/31/B/NZ6/02476 to RB), and Medical University of Bialystok (SUB/1/DN/20/003/1122 to EP). Part of the study was conducted with the use of equipment purchased by the Medical University of Białystok as part of the RPOWP 2007–2013 funding, Priority I, Axis 1.1, contract No. UDA- RPPD.01.01.00-20-001/15-00 dated June 26, 2015. This work was supported by the program of the Minister of Science and Higher Education under the name “Regional Initiative of Excellence in 2019–2022“, project number: 024/RID/2018/19, financing amount: 11.999.000,00 PLN. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Original Research

                Molecular medicine
                gold nanoparticles,ovarian cancer,gold nanopeanuts,anti-cancer therapy,nanotechnology,apoptosis,autophagy

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