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Molecules 2017, 22(7), 1080; doi:10.3390/molecules22071080

Fabrication and Cytotoxicity of Gemcitabine-Functionalized Magnetite Nanoparticles

1
Department of Life and Environmental Physics, “Horia Hulubei” National Institute for Physics and Nuclear Engineering, 30 Reactorului Street, Măgurele 077125, Romania
2
Department of Science and Engineering of Oxide Materials and Nanomaterials, Faculty of Applied Chemistry and Materials Science, University Politehnica of Bucharest, 1–7 Polizu Street, Bucharest 011061, Romania
3
Laboratory of Nanobiotechnology, National Institute for Research and Development in Microtechnologies, 12A Erou Iancu Nicolae Street, Bucharest 077190, Romania
4
Research Center for Microscopic Morphology and Immunology, University of Medicine and Pharmacy of Craiova, 2 Petru Rareș Street, Craiova 200349, Romania
5
Department of Pharmacognosy and Phytotherapy, Faculty of Pharmacy, University of Medicine and Pharmacy of Craiova, 2 Petru Rareș Street, Craiova 200349, Romania
*
Authors to whom correspondence should be addressed.
Received: 30 April 2017 / Revised: 10 June 2017 / Accepted: 21 June 2017 / Published: 28 June 2017

Abstract

Nanotechnology has been successfully used for the fabrication of targeted anti-cancer drug carriers. This study aimed to obtain Fe3O4 nanoparticles functionalized with Gemcitabine to improve the cytotoxic effects of the chemotherapeutic substance on cancer cells. The (un) functionalized magnetite nanoparticles were synthesized using a modified co-precipitation method. The nanoconjugate characterization was performed by XRD, SEM, SAED and HRTEM; the functionalizing of magnetite with anti-tumor substances has been highlighted through TGA. The interaction with biologic media has been studied by means of stability and agglomeration tendency (using DLS and Zeta Potential); also, the release kinetics of the drug in culture media was evaluated. Cytotoxicity of free-Gemcitabine and the obtained nanoconjugate were evaluated on human BT 474 breast ductal carcinoma, HepG2 hepatocellular carcinoma and MG 63 osteosarcoma cells by MTS. In parallel, cellular morphology of these cells were examined through fluorescence microscopy and SEM. The localization of the nanoparticles related to the cells was studied using SEM, EDX and TEM. Hemolysis assay showed no damage of erythrocytes. Additionally, an in vivo biodistribution study was made for tracking where Fe3O4@Gemcitabine traveled in the body of mice. Our results showed that the transport of the drug improves the cytotoxic effects in comparison with the one produced by free Gemcitabine for the BT474 and HepG2 cells. The in vivo biodistribution test proved nanoparticle accumulation in the vital organs, with the exception of spleen, where black-brown deposits have been found. These results indicate that our Gemcitabine-functionalized nanoparticles are a promising targeted system for applications in cancer therapy. View Full-Text
Keywords: magnetite nanoparticles; Gemcitabine; cancer therapy; in vitro cytotoxicity; biodistribution magnetite nanoparticles; Gemcitabine; cancer therapy; in vitro cytotoxicity; biodistribution
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Popescu, R.C.; Andronescu, E.; Vasile, B.Ș.; Truşcă, R.; Boldeiu, A.; Mogoantă, L.; Mogoșanu, G.D.; Temelie, M.; Radu, M.; Grumezescu, A.M.; Savu, D. Fabrication and Cytotoxicity of Gemcitabine-Functionalized Magnetite Nanoparticles. Molecules 2017, 22, 1080.

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