Graphene oxide as a drug carrier for delivery of zoledronic acid in secondary bone cancer treatment

Abstract

In this study, Zoledronic acid (ZOL), a type of nitrogen containing bisphosphonate, was loaded on graphene oxide (GO) particles to increase the particle size of the drug-nano-carrier complex which reduces drug ltration by the kidney and consequently, increases drug circulation time and its tumor uptake. The conjugation between ZOL and GO occurs via {u100000} stacking and hydrogen bonding interactions, and therefore, the drug may be gradually released from GO in physiological conditions which eliminates the need to apply high doses of the drug. Loading and release pro le of ZOL on GO particles was investigated by using UV-Vis spectroscopy. Samples with di erent concentrations of 0.025-1.25 mg/ml of ZOL were loaded on 0.2 mg/ml GO. UV analysis showed that the maximum loading happens at ZOL to GO ratio of 1:0.2. This loading was obtained when 1 mg/ml of ZOL was initially loaded on 0.2 mg/ml of GO nanoparticles. The drug and drug carrier complexes were characterized using Fourier-Transform Infrared Spectroscopy (FTIR), Atomic Force Microscopy (AFM), and UV-vis spectroscopy. Cell culture studies were carried out with MCF-7 breast cancer cells and mesenchymal stem cells (MSCs) for three dosages of ZOL, ZOL conjugated with GO (ZOL-GO) and GO. Cell proliferation was investigated by Alamar blue assay and cell viability was evaluated by staining dead cells with propidium iodide (PI) and live cells with acridine orange (AO). Overall, the characterization results con rm loading of ZOL on GO nanoparticles and cell studies results show that GO conjugated ZOL complexes are promising to reduce MCF-7 breast cancer cells proliferation and viability.|Keywords : ZOL, GO, Drug Loading, MCF-7, MSC.