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

Dong Li; Mingwu Deng; Ziyou Yu; Wei Liu; Guangdong Zhou; Wei Li; Xiansong Wang; Da-Peng Yang; Wenjie Zhang

doi:10.1021/acsbiomaterials.8b00029

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

ACS Biomater Sci Eng. 2018 Jun 11;4(6):2143-2154. doi: 10.1021/acsbiomaterials.8b00029. Epub 2018 May 9.

Authors

Dong Li¹, Mingwu Deng¹, Ziyou Yu¹, Wei Liu¹, Guangdong Zhou¹, Wei Li¹, Xiansong Wang¹, Da-Peng Yang², Wenjie Zhang¹

Affiliations

¹ Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Tissue Engineering, National Tissue Engineering Center of China, Shanghai 200011, China.
² Fujian Province Key Laboratory for Preparation and Function, Development of Active Substances from Marine Algae, College of Chemical Engineering and Materials Science, Quanzhou Normal University, Quanzhou 362000, P. R. China.

PMID: 33435038
DOI: 10.1021/acsbiomaterials.8b00029

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.

Keywords: iron oxides; magnetic particle imaging; nanoscale graphene oxide; targeted therapy.