Biocompatible and Stable GO-Coated Fe3O4 Nanocomposite: A Robust Drug Delivery Carrier for Simultaneous Tumor MR Imaging and Targeted Therapy.

Abstract

Combined targeted drug delivery and sustained drug release, through the application of nanomedicine, show great potential in cancer therapy and diagnostics. Systems based on folic acid conjugated with graphene oxide-based magnetic nanoparticles (NPs) show distinct advantages for such chemotherapeutic applications. Herein, we prepared FA-Fe3O4@nGO-DOX magnetic nanoparticles (MNPs) with a uniform size distribution based on nanoscale graphene oxide (nGO) encapsulated Fe3O4, which was conjugated with folic acid (FA) and loaded with doxorubicin (DOX). The prepared MNPs were characterized by various biophysical methods and featured a uniform size distribution. The uniform size of the nGO resulted in a relative narrow size distribution of the Fe3O4@nGO MNPs, which contributed to the stability of the nanocarrier system. Cell viability and in vitro biocompatibility studies of the FA-Fe3O4@nGO-DOX NPs revealed their selective uptake by MGC-803 cells. The relative viability was maintained at ∼90% after 48 h of incubation, and the hemolysis ratio confirmed the low toxicity of our modified NPs. The pH-controlled drug release and selective uptake of FA-Fe3O4@nGO NPs by MGC-803 cells via the FA receptor ensured selective killing of tumor cells. Furthermore, the nanoparticles for magnetic resonance imaging were analyzed in vitro and their signal intensity decreased as the NP concentration was increased. The nanocomposite was highly effective for in vivo imaging. Additionally, our in vivo antitumor activity and histological analysis confirmed the selective anticancer activity of the FA-Fe3O4@nGO-DOX NPs. Notably, our NPs were highly active and mice treated with FA-Fe3O4@nGO-DOX showed lower weight loss compared with mice treated with Fe3O4@nGO-DOX. More necrotic tissue was observed in the tumors of the FA-Fe3O4@nGO-DOX group compared with those observed in the control, Fe3O4@nGO-DOX, and DOX groups. Thus, FA-Fe3O4@nGO-DOX is an effective and stable candidate for targeted drug delivery.