The Synthesis and characterization of doxorubicin and bortezomib loaded magnetic nanoparticles for targeting tumor cells

Download
2013
Ünsoy, Gözde
Chitosan superparamagnetic nanoparticles, loaded with Doxorubicin and Bortezomib were synthesized for treatment of breast and cervical cancers by targeted drug delivery. In vitro cytotoxicity analyses revealed that the efficacy of drugs was highly increased when applied as loaded on nanoparticles. Chitosan superparamagnetic iron oxide nanoparticles (CSMNPs) were in-situ synthesized at different sizes by ionic crosslinking method. The characterization of nanoparticles was performed by XRD, XPS/ESCA, FTIR, TEM, DLS, TGA, VSM and zeta potential analyses. The XRD and XPS analyses proved that synthesized iron-oxide was magnetite (Fe3O4). Chitosan coating on the surface of magnetite was confirmed by FTIR. Average core size of CSMNPs were between 2-8 nm in TEM and hydrodynamic diameters were between 58-103 nm in DLS. TEM results demonstrated a spherical morphology. TGA results indicated that chitosan content of CSMNPs were between 15-23%. CSMNPs were found superparamagnetic by VSM analyses. The cellular uptake of nanoparticles was visualized by fluorescence microscopy and cytotoxicity was determined by XTT analyses on MCF-7, MCF-7/Dox, SiHa and HeLa cell lines. Doxorubicin and Bortezomib loading, release and stability efficiencies of CSMNPs were analyzed by considering the different parameters. CSMNPs are not cytotoxic without the drug load. When these drugs are loaded on CSMNPs, the antiproliferative efficiencies of drugs increases and resistance to these drugs is eliminated. IC50 values of drugs remarkably decreases when the drugs are given to the cells as loaded on CSMNPs. Proapoptotic Puma and Noxa genes were up regulated while antiapoptotic Bcl-2, Survivin and cIAP-2 genes were down regulated in drug loaded CSMNP treated cells. Consequently, CSMNPs synthesized at various sizes would be effectively used for the pH dependent release of Doxorubicin and Bortezomib. Results of this study can provide new insights in the development of pH responsive magnetic targeted drug delivery systems to overcome the side effects and resistance problem of conventional chemotherapy.

Suggestions

Synthesis and characterization of polymeric magnetic nanoparticles loaded by gemcitabine /
Parsian, Maryam; Gündüz, Ufuk; Tezcaner, Ayşen; Department of Biotechnology (2014)
In this study, different types of magnetic nanoparticles were synthesized for treatment of breast cancer by targeted drug delivery. Polyamidoamine (PAMAM) dendrimer, Chitosan (CS) and Polyhydroxybutyrate (PHB) coated magnetic nanoparticles were prepared and loaded with Gemcitabine. The loading efficiency of drug for various half generations of dendrimer coated magnetic nanoparticles (DcMNPs), Chitosan coated magnetic nanoparticles (CSMNPs) and Polyhydroxybutyrate magnetic nanoparticles (PHB-MNPs) were inves...
Synthesis of poly (dl-lactic-co-glycolic acid) coated magnetic nanoparticles for anti-cancer drug delivery
Tansık, Gülistan; Gündüz, Ufuk; Department of Biology (2012)
One of the main problems of current cancer chemotherapy is the lack of selectivity of anti-cancer drugs to tumor cells which leads to systemic toxicity and adverse side effects. In order to overcome these limitations, researches on controlled drug delivery systems have gained much attention. Nanoscale based drug delivery systems provide tumor targeting. Among many types of nanocarriers, superparamagnetic nanoparticles with their biocompatible polymer coatings can be targeted to an intented site by an extern...
The Preparation and characterization of dendrimer coated magnetic nanoparticles for targeted cancer therapy
Khodadust, Rouhollah; Gündüz, Ufuk; Gündüz, Güngör; Department of Biotechnology (2013)
Nanotechnology is a promising alternative to overcome the limitations of classical chemotherapy. This technology has enabled the development of particles with nano sizes that can be fabricated from a multitude of materials in a variety of compositions. These nanoparticles include; quantum dots (QDs), polymeric nanoparticles, gold nanoparticles, magnetic nanoparticles and dendrimeric nanoparticles. In first section of this study, superparamagnetic iron oxide nanoparticles were synthesized by coprecipitation ...
Development of poly (I:C) modified doxorubicin loaded magnetic dendrimer nanoparticles for targeted combination therapy
Khodadust, Rouhollah; Unsoy, Gozde; Gündüz, Ufuk (2014-10-01)
The objective of this study was to develop and evaluate the anticancer activity and the safety of a combinational drug delivery system using polyamidoamine (PAMAM) dendrimer-coated iron oxide nanoparticles for doxorubicin and poly I:C delivery in vitro. Dendrimer-coated magnetic nanoparticles (DcMNPs) are suitable for drug delivery system as nanocarriers with their following properties, such as surface functional groups, symmetry perfection, internal cavities, nano-size and magnetization. These nanoparticle...
INVESTIGATION OF CLONAL EVOLUTION IN CAPECITABINE RESISTANT CACO-2 AND IRINOTECAN RESISTANT HT-29 CELL LINES BY USING CELLULAR BARCODING TECHNOLOGY
Danışık, Nurseda; Acar, Ahmet; Özen, Can; Department of Biotechnology (2022-10-31)
The development of drug resistance in tumor cells is one of the biggest problems currently in the clinic. As the pace of drug discovery slows and each new drug becomes increasingly expensive to bring to market, it is becoming clearer that better model systems and an understanding of drug resistance mechanisms are needed for second-line therapies. The overall aim of this project is to investigate the clonal evolution and drug resistance in colorectal cancer cell lines Caco-2 and HT-29 by using cellular barco...
Citation Formats
G. Ünsoy, “The Synthesis and characterization of doxorubicin and bortezomib loaded magnetic nanoparticles for targeting tumor cells,” Ph.D. - Doctoral Program, Middle East Technical University, 2013.