Fabrication and Cytotoxicity of Gemcitabine-Functionalized Magnetite Nanoparticles

• Published in: Molecules (Basel, Switzerland) Vol. 22; no. 7; p. 1080
• Main Authors: Popescu, Roxana Cristina, Andronescu, Ecaterina, Vasile, Bogdan Ștefan, Truşcă, Roxana, Boldeiu, Adina, Mogoantă, Laurențiu, Mogoșanu, George Dan, Temelie, Mihaela, Radu, Mihai, Grumezescu, Alexandru Mihai, Savu, Diana
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 28.06.2017; MDPI
• Subjects: Antineoplastic Agents - adverse effects; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Biocompatibility; Biomedical materials; Cancer; Carcinoma, Hepatocellular - metabolism; Cell culture; Cell Line, Tumor; Cell Survival - drug effects; Culture media; Cytotoxicity; Deoxycytidine - adverse effects; Deoxycytidine - analogs & derivatives; Deoxycytidine - chemistry; Deoxycytidine - pharmacology; Drug carriers; Drug delivery; Erythrocytes; Erythrocytes - drug effects; Fabrication; Fluorescence; Fluorescence microscopy; Gemcitabine; Hep G2 Cells; Hepatocellular carcinoma; Humans; In vivo methods and tests; Iron oxides; Kinetics; Liver Neoplasms - metabolism; Localization; Magnetite; Magnetite Nanoparticles - chemistry; Nanoparticles; Nanotechnology; Nanotechnology - methods; Organs; Osteosarcoma; Osteosarcoma cells; Spleen; Zeta potential; in vitro cytotoxicity; cancer therapy; biodistribution; magnetite nanoparticles; Gemcitabine
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules22071080

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.