Graphene oxide (GO) nanoparticles have been developed for a variety of biomedical applications as a number of different therapeutic modalities may be added onto them. Here, we report the development and testing of such a multifunctional GO nanoparticle platform that contains a grafted cell-targeting functionality, active pharmaceutical ingredients, and particulates that enable the use of magnetothermal therapy. Specifically, we demonstrate the ability to covalently attach hyaluronic acid (HA) onto GO, and the resultant nanoparticulates (GO-HA) exhibited low inherent toxicity toward two different breast cancer cell lines, BT-474 and MDA-MB-231. Doxorubicin (Dox) and paclitaxel (Ptx) were successfully loaded onto GO-HA with high and moderate efficiencies, respectively. A GO-HA-Dox/Ptx system was significantly better than the GO-Dox/Ptx system at specifically killing CD44-expressing MDA-MB-231 cells but not BT-474 cells that do not express CD44. Further, modified iron oxide nanoparticles were loaded onto the GO-HA-Dox system, enabling the use of magnetic hyperthermia. Hyperthermia in combination with Dox treatment through the GO-HA system showed significantly better performance in reducing viable tumor cell numbers when compared to the individual systems. In summary, we showcase a multifunctional GO nanoparticle system that demonstrates improved efficacy in killing tumor cells.
The study presented in this work consists of two parts: The first part is the synthesis of Graphene oxide-Fe3O4 nanocomposites by a mechanochemical method which, is a mechanical process that is likely to yield extremely heterogeneous particles. The second part includes a study on the efficacy of these Graphene oxide-Fe3O4 nanocomposites to kill cancerous cells. Iron powder, ball milled along with graphene oxide in a toluene medium, underwent a controlled oxidation process. Different phases of GO-Fe3O4 nanocomposites were obtained based on the composition used for milling. As synthesized nanocomposites were characterized by x-ray diffraction (XRD), alternating magnetic field (AFM), Raman spectroscopy, and a vibrating sample magnetometer (VSM). Additionally, the magnetic properties required to obtain high SAR values (Specific Absorption Rate-Power absorbed per unit mass of the magnetic nanocomposite in the presence of an applied magnetic field) for the composite were optimized by varying the milling time. Nanocomposites milled for different extents of time have shown differential behavior for magneto thermic heating. The magnetic composites synthesized by the ball milled method were able to retain the functional groups of graphene oxide. The efficacy of the magnetic nanocomposites for killing of cancerous cells is studied in vitro using HeLa cells in the presence of an AC (Alternating Current) magnetic field. The morphology of the HeLa cells subjected to 10 min of AC magnetic field changed considerably, indicating the death of the cells.
The integration of zinc ferrite coatings on helical magnetic nanomotors provides long-term stability against agglomeration and therapeutic magnetic hyperthermia potential.