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Cytotoxicity and Physicochemical Characterization of Iron–Manganese-Doped Sulfated Zirconia Nanoparticles

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Cytotoxicity and Physicochemical Characterization of Iron–Manganese-Doped Sulfated Zirconia Nanoparticles Journal name: International Journal of Nanomedicine Article Designation: Original Research Year: 2015 Volume: 10 International Journal of Nanomedicine Dovepress Running head verso: Al-Fahdawi et al Running head recto: Iron–manganese-doped sulfated zirconia nanoparticles open access to scientific and medical research DOI: http://dx.doi.org/10.2147/IJN.S82586 Open Access Full Text Article ORIGINAL RESEARCH Cytotoxicity and physicochemical characterization of iron–manganese-doped sulfated zirconia nanoparticles Mohamed Qasim Abstract: Iron–manganese-doped sulfated zirconia nanoparticles with both Lewis and Brønsted Al-Fahdawi1 acidic sites were prepared by a hydrothermal impregnation method followed by calcination at Abdullah Rasedee1,2 650°C for 5 hours, and their cytotoxicity properties against cancer cell lines were determined. Mothanna Sadiq Al-Qubaisi1 The characterization was carried out using X-ray diffraction, thermogravimetric analysis, Fourier Fatah H Alhassan3,4 transform infrared spectroscopy, Brauner–Emmett–Teller (BET) surface area measurements, Rozita Rosli1 X-ray fluorescence, X-ray photoelectron spectroscopy, zeta size potential, and transmission electron microscopy (TEM). The cytotoxicity of iron–manganese-doped sulfated zirconia nano- Mohamed Ezzat El particles was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide Zowalaty1,5 (MTT) assays against three human cancer cell lines (breast cancer MDA-MB231 cells, colon 6 Seïf-Eddine Naadja carcinoma HT29 cells, and hepatocellular carcinoma HepG2 cells) and two normal human 7,8 Thomas J Webster cell lines (normal hepatocyte Chang cells and normal human umbilical vein endothelial cells 3,4 Yun Hin Taufiq-Yap [HUVECs]). The results suggest for the first time that iron–manganese-doped sulfated zirconia 1Institute of Bioscience, 2Department nanoparticles are cytotoxic to MDA-MB231 and HepG2 cancer cells but have less toxicity to of Veterinary Pathology and HT29 and normal cells at concentrations from 7.8 μg/mL to 500 μg/mL. The morphology of Microbiology, Faculty of Veterinary Medicine, 3Catalysis Science and the treated cells was also studied, and the results supported those from the cytotoxicity study Technology Research Centre, Faculty in that the nanoparticle-treated HepG2 and MDA-MB231 cells had more dramatic changes in 4 of Science, Department of Chemistry, cell morphology than the HT29 cells. In this manner, this study provides the first evidence that Faculty of Science, 5Biomedical Research Center, Qatar University, iron–manganese-doped sulfated zirconia nanoparticles should be further studied for a wide range Doha, Qatar; 6Department of Cell of cancer applications without detrimental effects on healthy cell functions. and Molecular Biology, Faculty of nanopartices, Lewis and Brønsted acidic sites, anticancer applications, HT29 cells, Biotechnology and Biomolecular Keywords: Sciences, Universiti Putra Malaysia transition metal oxide (UPM), Serdang, Selangor, Malaysia; 7Department of Chemical Engineering, Northeastern University, Boston, Introduction 8 MA, USA; Center of Excellence for Many processes which are very significant to life (such as pharmaceutical and Advanced Materials Research, King Abdulaziz University, Jeddah, Saudi petrochemical processes) have benefited from solid acid enhancers leading to improve- Arabia ments in selectivity and activity.1,2 It has been reported that the status of active sites on a material surface, whether it is of Brønsted or Lewis nature, are common factors for promoting bioactivity and bioselectivity. In this respect, the incorporation of pow- erful acidic anions on the surface of various material supporting structures (such as 3 Correspondence: Abdullah Rasedee alumina, silica, and zirconia) has attracted great attention. Among the most powerful Department of Veterinary Pathology acidic anions, sulfate species doped on the surface of zirconium oxide have gener- and Microbiology, Faculty of Veterinary ated great potential for a number of significant processes such as organic synthesis.4 Medicine, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia Nevertheless, the selectivity and activity of nanoparticles of iron(+3)–manganese-doped Tel +603 8946 3455 sulfated zirconia can be governed by the effective incorporation of ferric oxide and Fax +603 8946 1971 Email [email protected] manganese dioxide as well as sulfate anions into the zirconia skeleton.5 They display submit your manuscript | www.dovepress.com International Journal of Nanomedicine 2015:10 5739–5750 5739 Dovepress © 2015 Al-Fahdawi 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 http://dx.doi.org/10.2147/IJN.S82586 permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php Al-Fahdawi et al Dovepress the best catalytic activity toward n-butane isomerization The development of chemical target agents that exploit dif- under reasonable conditions.6 ferences between cancerous and normal cells permits greater Along the same lines, nanoparticle medications have specificity for cancer cells with less damage to normal healthy arisen as a modern research direction for the release of cells.34 Although chemotherapy and radiation therapy can hydrophobic medicines owing to their characteristic gains induce cancer remission in patients with tumors, a group of over colloidal drug transporters.7 Generally, transition metal malignancies remains a therapeutic challenge due to frequent oxides have been commonly employed either as supporters tumor relapse and chemotherapy resistance.35 Thus, there is a or as promoters to improve physiochemical properties for continual need to identify drugs which are nontoxic, have few many reactions.8–11 For example, approximately all advanced adverse side effects, and might be of great benefit in reducing materials contain an oxide as the active system which shows the dosage of existing chemotherapeutic drugs. both hydrogen ion and electron transmission abilities and Doxorubicin is one of the best drugs for systemic chemo- should be utilized as an enhancer in acid–base reactions as therapy which works against breast cancer. For colon cancer well as electron gain and release reactions. These reduction– treatment, oxaliplatin is commonly used, while tamoxifen is oxidation processes utilizing metal oxide redox properties the most commonly used drug for liver cancer.33,35 have been widely applied as an environmentally friendly The evidence currently available clearly indicates that sul- process for the full oxidation of polluted ingredients.12–19 fated zirconia nanoparticles are toxic in vitro for several types Moreover, transition metal oxide systems having redox of cancer cells including human colorectal carcinoma HT29 properties are also used for the conversion of organic cells, human liver carcinoma HepG2 cells, and human breast constituent sustainable and renewable chemicals.20–22 The carcinoma MCF-7 cells. In contrast, normal (noncancerous) physicochemical properties of transition metal oxides are human breast carcinoma MCF-10a cells were found to be the considered to be a potential factor in carrying out discriminat- least sensitive to sulfated zirconia nanoparticles.36 ing organic reactions. Meanwhile, the rate-determining step As far as it is known, the present in vitro study is the first on the surface of such novel materials would be evaluated report to determine the anticancer properties of iron–man- via the mass of energetic sites in addition to the Brauner– ganese-doped sulfated zirconia nanoparticles. The addition Emmett–Teller (BET) surface area with notable improve- of iron will help the directed delivery (via magnetic force) ments in catalytic activity related to increases in BET surface of nanoparticles to cancer sites. Iron(+3)–manganese-doped area that comes from smaller particle diameters. Thus, in the sulfated zirconia nanoparticles were synthesized in this study emerging field of nanoparticles, the synthesis of transition via a hydrothermal impregnation method and were character- metal oxide nanoparticles has garnered significant consider- ized using X-ray photoelectron spectroscopy, X-ray diffrac- ation, attributable to unique physical and chemical properties tion (XRD), thermogravimetric analysis, Fourier transform gained for materials at the nanoscale.23,24 infrared spectroscopy, BET, X-ray fluorescence, zeta size The surface of zirconia is known to have all of these potential, and transmission electron microscopy (TEM). The physicochemical properties. Doping ZrO2 with materials such toxicity of iron–manganese-doped sulfated zirconia nanopar- as ferric, manganese, nickel, platinum, phosphate, and sulfate ticles was assessed here against human colon cancer HT29 species has significantly improved its catalytic activity.25–27 cells, human breast cancer MDA-MB231 cells, and human In particular, iron(+3)–manganese-doped sulfated zirconia liver cancer HepG2 cells in comparison with oxaliplatin, has been commonly employed to enhance various life- doxorubicin, and tamoxifen, respectively. Normal (noncan- support
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