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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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      Enhanced antitumor activity of surface-modified iron oxide nanoparticles and an α-tocopherol derivative in a rat model of mammary gland carcinosarcoma

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          Abstract

          Maghemite (γ-Fe 2O 3) nanoparticles were obtained by coprecipitation of ferrous and ferric salts in an alkaline medium followed by oxidation; the nanoparticles were coated with poly( N,N-dimethylacrylamide) (PDMA) and characterized by transmission electron microscopy, attenuated total reflection (ATR) Fourier transform infrared (FTIR) spectroscopy, dynamic light scattering, thermogravimetric and elemental analyses, and magnetic measurements in terms of particle morphology, size, polydispersity, amount of coating, and magnetization, respectively. The effects of α-tocopherol (Toc) and its phenolic (Toc-6-OH) and acetate (Toc-6-Ac) derivatives on Fe 2+ release from γ-Fe 2O 3@PDMA, as well as from γ-Fe 2O 3 and CuFe 2O 4 nanoparticles (controls), were examined in vitro using 1,10-phenanthroline. The presence of tocopherols enhanced spontaneous Fe 2+ release from nanoparticles, with Toc-6-OH exhibiting more activity than neat Toc. All of the nanoparticles tested were found to initiate blood lipid oxidation in a concentration-dependent manner, as determined by analysis of 2-thiobarbituric acid reactive species. Wistar rats with Walker-256 carcinosarcoma (a model of mammary gland carcinosarcoma) received Toc-6-Ac, magnetic nanoparticles, or their combination per os, and the antitumor activity of each treatment was determined in vivo. γ-Fe 2O 3@PDMA nanoparticles exhibited increased antitumor activity compared to both commercial CuFe 2O 4 particles and the antitumor drug doxorubicin. Moreover, increased antitumor activity was observed after combined administration of γ-Fe 2O 3@PDMA nanoparticles and Toc-6-Ac; however, levels of bilirubin, aspartate aminotransferase, and white bloods normalized and did not differ from those of the intact controls. The antitumor activity of the γ-Fe 2O 3 nanoparticles strongly correlated with Fe 2+ release from the nanoparticles but not with nanoparticle-initiated lipid peroxidation in vitro.

          Most cited references62

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          Iron and cancer: more ore to be mined.

          Iron is an essential nutrient that facilitates cell proliferation and growth. However, iron also has the capacity to engage in redox cycling and free radical formation. Therefore, iron can contribute to both tumour initiation and tumour growth; recent work has also shown that iron has a role in the tumour microenvironment and in metastasis. Pathways of iron acquisition, efflux, storage and regulation are all perturbed in cancer, suggesting that reprogramming of iron metabolism is a central aspect of tumour cell survival. Signalling through hypoxia-inducible factor (HIF) and WNT pathways may contribute to altered iron metabolism in cancer. Targeting iron metabolic pathways may provide new tools for cancer prognosis and therapy.
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            Superparamagnetic iron oxide nanoparticles (SPIONs): development, surface modification and applications in chemotherapy.

            At present, nanoparticles are used for various biomedical applications where they facilitate laboratory diagnostics and therapeutics. More specifically for drug delivery purposes, the use of nanoparticles is attracting increasing attention due to their unique capabilities and their negligible side effects not only in cancer therapy but also in the treatment of other ailments. Among all types of nanoparticles, biocompatible superparamagnetic iron oxide nanoparticles (SPIONs) with proper surface architecture and conjugated targeting ligands/proteins have attracted a great deal of attention for drug delivery applications. This review covers recent advances in the development of SPIONs together with their possibilities and limitations from fabrication to application in drug delivery. In addition, the state-of-the-art synthetic routes and surface modification of desired SPIONs for drug delivery purposes are described. Copyright © 2010 Elsevier B.V. All rights reserved.
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              Oral drug delivery with polymeric nanoparticles: the gastrointestinal mucus barriers.

              Oral delivery is the most common method for drug administration. However, poor solubility, stability, and bioavailability of many drugs make achieving therapeutic levels via the gastrointestinal (GI) tract challenging. Drug delivery must overcome numerous hurdles, including the acidic gastric environment and the continuous secretion of mucus that protects the GI tract. Nanoparticle drug carriers that can shield drugs from degradation and deliver them to intended sites within the GI tract may enable more efficient and sustained drug delivery. However, the rapid secretion and shedding of GI tract mucus can significantly limit the effectiveness of nanoparticle drug delivery systems. Many types of nanoparticles are efficiently trapped in and rapidly removed by mucus, making controlled release in the GI tract difficult. This review addresses the protective barrier properties of mucus secretions, how mucus affects the fate of orally administered nanoparticles, and recent developments in nanoparticles engineered to penetrate the mucus barrier. Copyright © 2011 Elsevier B.V. All rights reserved.
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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
                06 June 2017
                : 12
                : 4257-4268
                Affiliations
                [1 ]Department of Polymer Particles, Institute of Macromolecular Chemistry AS CR, Prague, Czech Republic
                [2 ]Department of Vitamins and Coenzyme Biochemistry, Palladin Institute of Biochemistry, NASU, Ukraine
                [3 ]Department of Mechanisms of Antitumor Therapy, R. E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NASU, Ukraine
                Author notes
                Correspondence: Daniel Horák, Department of Polymer Particles, Institute of Macromolecular Chemistry AS CR, Heyrovsky Sq 2, 162 06 Prague 6, Czech Republic, Tel +420 29680 9260, Fax +420 29680 9410, Email horak@ 123456imc.cas.cz
                Article
                ijn-12-4257
                10.2147/IJN.S137574
                5473599
                848e2664-4245-461c-9ebf-b5e5d1e03292
                © 2017 Horák 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
                iron oxide nanoparticles,poly(n,n-dimethylacrylamide),lipid oxidation,oxidative stress,antitumor activity,α-tocopherol

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