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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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      The influence of female mice age on biodistribution and biocompatibility of citrate-coated magnetic nanoparticles

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          Abstract

          Background

          Magnetic nanoparticles (MNPs) have been successfully tested for several purposes in medical applications. However, knowledge concerning the effects of nanostructures on elderly organisms is remarkably scarce.

          Purpose

          To fill part of this gap, this work aimed to investigate biocompatibility and bio-distribution aspects of magnetic nanoparticles coated with citrate (NpCit) in both elderly and young healthy mice.

          Methods

          NpCit (2.4 mg iron) was administered intraperitoneally, and its toxicity was evaluated for 28 days through clinical, biochemical, hematological, and histopathological examinations. In addition, its biodistribution was evaluated by spectrometric (inductively coupled plasma optical emission spectrometry) and histological methods.

          Results

          NpCit presented age-dependent effects, inducing very slight and temporary biochemical and hematological changes in young animals. These changes were even weaker than the effects of the aging process, especially those related to the hematological data, tumor necrosis factor alpha, and nitric oxide levels. On the other hand, NpCit showed a distinct set of results in the elderly group, sometimes reinforcing (decrease of lymphocytes and increase of monocytes) and sometimes opposing (erythrocyte parameters and cytokine levels) the aging changes. Leukocyte changes were still observed on the 28th day after treatment in the elderly group. Slight evidence of a decrease in liver and immune functions was detected in elderly mice treated or not treated with NpCit. It was noted that tissue damage or clinical changes related to aging or to the NpCit treatment were not observed. As detected for aging, the pattern of iron biodistribution was significantly different after NpCit administration: extra iron was detected until the 28th day, but in different organs of elderly (liver and kidneys) and young (spleen, liver, and lungs) mice.

          Conclusion

          Taken together, the data show NpCit to be a stable and reasonably biocompatible sample, especially for young mice, and thus appropriate for biomedical applications. The data showed important differences after NpCit treatment related to the animals’ age, and this emphasizes the need for further studies in older animals to appropriately extend the benefits of nanotechnology to the elderly population.

          Most cited references60

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          Oxidants, antioxidants, and the degenerative diseases of aging.

          Metabolism, like other aspects of life, involves tradeoffs. Oxidant by-products of normal metabolism cause extensive damage to DNA, protein, and lipid. We argue that this damage (the same as that produced by radiation) is a major contributor to aging and to degenerative diseases of aging such as cancer, cardiovascular disease, immune-system decline, brain dysfunction, and cataracts. Antioxidant defenses against this damage include ascorbate, tocopherol, and carotenoids. Dietary fruits and vegetables are the principal source of ascorbate and carotenoids and are one source of tocopherol. Low dietary intake of fruits and vegetables doubles the risk of most types of cancer as compared to high intake and also markedly increases the risk of heart disease and cataracts. Since only 9% of Americans eat the recommended five servings of fruits and vegetables per day, the opportunity for improving health by improving diet is great.
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            Nanoparticles for drug delivery in cancer treatment.

            Nanoparticles (size in nanometer range) provide a new mode of cancer drug delivery functioning as a carrier for entry through fenestrations in tumor vasculature allowing direct cell access. These particles allow exquisite modification for binding to cancer cell membranes, the microenvironment, or to cytoplasmic or nuclear receptor sites. This results in delivery of high drug concentrations to the targeted cancer cell, with reduced toxicity of normal tissue. Several such engineered drugs are in clinical practice, including liposomal doxorubicin and albumin conjugate paclitaxel. The carrier mediated paclitaxel has already shown significant efficacy in taxane resistant cancers, an approach highly relevant in prostate cancer, where taxanes are the treatment of choice. Other modifications including transferrin receptor and folate receptor targeted drug delivery molecules are in study. This new technology provides many exciting therapeutic approaches for targeted high concentration drug delivery to cancer cells with reduced injury of normal cells.
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              Liver diseases and aging: friends or foes?

              The liver is the only internal human organ capable of natural regeneration of lost tissue, as little as 25% of a liver can regenerate into a whole liver. The process of aging predisposes to hepatic functional and structural impairment and metabolic risk. Therefore, understanding how aging could affect the molecular pathology of liver diseases is particularly important, and few studies to date have tackled this complex process. The most common liver disease, affecting one-third of the overall population, is nonalcoholic fatty liver disease (NAFLD), characterized by an intrahepatic accumulation of lipids. NAFLD can evolve into nonalcoholic steatohepatitis (NASH) in the presence of oxidative stress and inflammation. NASH is a serious risk factor for disabling and deadly liver diseases such as cirrhosis and hepatocellular carcinoma (HCC). Old age seems to favor NAFLD, NASH, and ultimately HCC, in agreement with the inflamm-aging theory, according to which aging accrues inflammation. However, the incidence of HCC drops significantly in the very elderly (individuals aged more than 70) and the relationship between the progression of NAFLD/NASH/HCC and very old age is obscure. In this review, we discuss the literature and we argue that there might be an age window in which the liver becomes resistant to the development of injury; this needs to be studied to understand fully the interaction between age and liver diseases from a therapeutic perspective. © 2013 the Anatomical Society and John Wiley & Sons Ltd.
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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
                2019
                08 May 2019
                : 14
                : 3375-3388
                Affiliations
                [1 ]Department of Genetics and Morphology, Institute of Biological Sciences, CNANO, University of Brasilia, Brasilia, DF 70910-900, Brazil, zulmira@ 123456unb.br
                [2 ]Post-graduation Program in Molecular Pathology, Faculty of Medicine, University of Brasilia, Brasília, DF 70910-900, Brazil, zulmira@ 123456unb.br
                [3 ]Laboratory of Immunology and Inflammation, Department of Cell Biology, University of Brasilia, Brasilia, DF 70910-900, Brazil
                [4 ]Green Nanotechnology Group, Faculty of Ceilandia, University of Brasilia, Brasília, DF 72220-900, Brazil
                Author notes
                Correspondence: Zulmira GM Lacava, Department of Genetics and Morphology, Institute of Biological Sciences, CNANO, University of Brasilia, Brasília, DF 70910-900, Brazil, Tel +55 6 1 3107-3081, Email zulmira@ 123456unb.br
                Article
                ijn-14-3375
                10.2147/IJN.S197888
                6511116
                31123402
                ee2d7c2d-65ab-401f-92cd-3987aedf4f6a
                © 2019 Pinheiro 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
                elderly,nanotoxicity,maghemite nanoparticles,superparamagnetic iron oxide nanoparticles,spio,nano-safety,inductively coupled plasma optical emission spectrometry,icp-oes

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