Synthesis and characterization of polyethylene glycol coated magnetic nanoparticles and their use for anti-cancer drug delivery

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2014
Erdem, Murat
Although conventional chemotherapy is the most valid method to cope with cancer, it has many drawbacks such as decrease in production of blood cells, inflammation of the lining of the digestive tract, hair loss etc. Reasons for its side effects are that drugs used in chemotherapy are distributed evenly within the body of a patient and cannot distinguish the cancer cells from the healthy ones. To decrease the negative effects of chemotherapeutic drugs and to increase their efficiency, many drug delivery systems have been developed until now. Magnetic nanoparticles have an important potential for cancer treatment. The most significant feature of magnetic nanoparticles is that they can be manipulated for targeting to tumor side by application of external magnetic field. Also, their small size and their capability to carry drug by surface modification are other important characteristics for drug delivery. Aim of this study is to synthesize folic acid conjugated, polyethylene coated magnetic nanoparticles (FA-MNPs) and doxorubicin loaded formulation (Dox-FA-MNPs), and to vi investigate their cytotoxicity on HeLa and doxorubicin resistant HeLa cells. Magnetic nanoparticles (MNPs), PEG coated MNPs and FA-MNPs were successfully synthesized and characterized by one or more of TEM, FTIR, XRD, TGA and VSM analysis. Doxorubicin (Dox) loading capacity of FA-MNPs and release profile of Dox from Dox-FA-MNPs were investigated by spectrometer. Internalization of FA-MNPs and Dox-FA-MNPs by HeLa cells were observed by purssian blue staining under light microscopy and by using fluorescent property of Dox under fluorescent microscopy respectively. Biocompatibility of FA-MNPs and antiproliferative effects of Dox-FA-MNPs on HeLa and HeLa/Dox cells were analyzed by XTT cell proliferation assay. The results show that synthesis of MNPs, PEG-MNPs and FA-MNPs were successfully achieved. MNPs had a special shape and small size and also had supermagnetic behavior. 505 μM of 1724 μM Dox was loaded 500 μg/mL FA-MNPs and in 24 h, 68,35 μM Dox was released from 500 μg/mL Dox-FA-MNPs. Also, drug release was increased in acidic condition from Dox-FA-MNPs. Internalization experiments showed that FA-MNPs and Dox-FA-MNPs were taken up by HeLa cells. FA-MNPs and Dox-FA-MNPs were given to HeLa and HeLa/Dox cells for investigation of their cytotoxicities. Cell proliferation assay results showed that Dox-FA-MNPs significantly decreased the proliferation of HeLa cells when compared to FA-MNPs. However, Dox-FA-MNPs did not show same effects on HeLa/Dox cells. Despite that Dox-FA-MNPs could not overcome drug resistance of HeLa/Dox cells, they effectively killed HeLa cells. As a result, FA-MNPs have found to be important for carrying Dox.

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Citation Formats
M. Erdem, “Synthesis and characterization of polyethylene glycol coated magnetic nanoparticles and their use for anti-cancer drug delivery,” M.S. - Master of Science, Middle East Technical University, 2014.