Abstract

Zoledronic acid (ZOL) is a third generation bisphosphonate which can be used as a drug for the treatment of osteoporosis and metastasis. In this study, graphene oxide (GO) is conjugated with ZOL, and the nanostructured material is evaluated in terms viability, proliferation and differentiation. Furthermore, the associated morphological changes of bone marrow-derived mesenchymal stem cells (BM-MSC), and Michigan Cancer Foundation-7 (MCF-7) breast cancer cells, as well as the effect of the drugs on mineralization of BM-MSCs are investigated using a variety of characterization techniques including Fourier Transform Infrared Spectroscopy (FTIR), scanning electron microscopy (SEM) as well as alamar blue, acridine orange, and alizarin red assays. Nanostructured ZOL-GO with an optimum performance is synthesized using ZOL and GO suspensions with the concentration of 50 µM and 2.91 ng/ml, respectively. ZOL-GO nanostructures can facilitate the mineralization of BM-MSC cells, demonstrated by the formation of clusters around the cells. The results obtained confirm the performance of ZOL-GO nanostructures as promising drug complexes for the treatment of osteoporosis and metastasis.

Highlights

  • Zoledronic acid (ZOL) is a third generation bisphosphonate which can be used as a drug for the treatment of osteoporosis and metastasis

  • Different concentrations of graphene oxide (GO) were loaded on ZOL, and the effects of ZOL, GO and ZOL-GO complexes on the characteristics of the bone marrow-derived mesenchymal stem cells (BM-MSC) and Michigan Cancer Foundation-7 (MCF-7) cell lines were studied

  • Both ZOL and ZOL-GO complexes significantly decreased the viability of MCF-7 cells

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Summary

Introduction

Zoledronic acid (ZOL) is a third generation bisphosphonate which can be used as a drug for the treatment of osteoporosis and metastasis. Graphene oxide (GO), carbon nanotubes (CNT), nanodiamond and carbon black are known to be capable of delivering drugs into cancer cells, improving the efficiency of the drug[23]. Among these carbons, GO has obvious advantages such as low cost, the presence of two external chemically active surfaces, easy fabrication and modification, and the absence of toxic metal particles during its production[24]. GO has been used as a drug carrier for anti-cancer drugs such as doxorubicin[29], camptothecin[30], paclitaxel[31], pirfenidone[32] and adriamycin[30,33] Since both GO and ZOL contain aromatic rings in their chemical structure, ZOL could conjugate with GO by non-covalent π − π interactions. The prepared complex significantly increased the degree of mineralization of BM-MSCs

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