Abstract
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.
Highlights
Graphene oxide (GO)-based nanomaterials have shown tremendous promise in controlled delivery of therapeutic agents.[1−3] The unique physicochemical properties of GO such as its large surface area, its ability to interact with and adsorb hydrophobic molecules, and its relative inertness to biological substances make it an ideal choice as a base material for drug delivery.[1,4,5] A number of drug delivery systems utilizing GO are being developed, and a significant majority of these systems focus on their use for delivering chemotherapeutics.[4,5] like many other systems, GO-based delivery of chemotherapeutics suffers from the inability to target specific cells in the body
We demonstrate the successful synthesis of graphene oxide particulates and show that they may be used as a platform for the addition of multiple functionalities
We demonstrate that hyaluronic acid may be grafted onto GO, and chemotherapeutic drugs may be loaded onto these particles to enable killing of tumor cells
Summary
Graphene oxide (GO)-based nanomaterials have shown tremendous promise in controlled delivery of therapeutic agents.[1−3] The unique physicochemical properties of GO such as its large surface area, its ability to interact with and adsorb hydrophobic molecules, and its relative inertness to biological substances make it an ideal choice as a base material for drug delivery.[1,4,5] A number of drug delivery systems utilizing GO are being developed, and a significant majority of these systems focus on their use for delivering chemotherapeutics.[4,5] like many other systems, GO-based delivery of chemotherapeutics suffers from the inability to target specific cells in the body. The higher burst release in an acidic environment could possibly be due to lowered hydrogen bonding between the amine group of DOX molecules and the hydroxyl group of graphene oxide nanoparticles These results suggest that, in extracellular spaces (or in the blood), a limited amount of drug would be released from these particulates, and a larger portion of the drug would release only upon the intracellular uptake of the nanoparticulates. When tested on MDA-MB-231 (CD44-expressing cells), GOHA was found to be significantly better at reducing the number of viable cells when compared to GO at high concentrations (Figure 6B) This difference is likely due to HA conjugation, which is thought to improve the interaction and uptake of GO-. We suggest that this difference could be a result of improved uptake of GO-
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