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Open AccessArticle

Magnetic Graphene Oxide for Dual Targeted Delivery of Doxorubicin and Photothermal Therapy

1
Department of Neurosurgery, Chang Gung Memorial Hospital Linkuo Medical Center and College of Medicine, Chang Gung University, Taoyuan 33305, Taiwan
2
Department of Chemical and Materials Engineering, Chang Gung University, Taoyuan 33302, Taiwan
3
Department of Plastic and Reconstructive Surgery and Craniofacial Research Center, Chang Gung Memorial Hospital, Linkou, Kwei-San, Taoyuan 33305, Taiwan
4
Research Center for Food and Cosmetic Safety, Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Kwei-San, Taoyuan 33302, Taiwan
5
Department of Materials Engineering, Ming Chi University of Technology, Tai-Shan, New Taipei City 24301, Taiwan
*
Author to whom correspondence should be addressed.
Nanomaterials 2018, 8(4), 193; https://doi.org/10.3390/nano8040193
Received: 2 March 2018 / Revised: 23 March 2018 / Accepted: 23 March 2018 / Published: 27 March 2018
(This article belongs to the Special Issue Nanocolloids for Nanomedicine and Drug Delivery)
To develop a pH-sensitive dual targeting magnetic nanocarrier for chemo-phototherapy in cancer treatment, we prepared magnetic graphene oxide (MGO) by depositing Fe3O4 magnetic nanoparticles on graphene oxide (GO) through chemical co-precipitation. MGO was modified with polyethylene glycol (PEG) and cetuximab (CET, an epidermal growth factor receptor (EGFR) monoclonal antibody) to obtain MGO-PEG-CET. Since EGFR was highly expressed on the tumor cell surface, MGO-PEG-CET was used for dual targeted delivery an anticancer drug doxorubicin (DOX). The physico-chemical properties of MGO-PEG-CET were fully characterized by dynamic light scattering, transmission electron microscopy, X-ray diffraction, Fourier transform Infrared spectroscopy, thermogravimetric analysis, and superconducting quantum interference device. Drug loading experiments revealed that DOX adsorption followed the Langmuir isotherm with a maximal drug loading capacity of 6.35 mg/mg, while DOX release was pH-dependent with more DOX released at pH 5.5 than pH 7.4. Using quantum-dots labeled nanocarriers and confocal microscopy, intracellular uptakes of MGO-PEG-CET by high EGFR-expressing CT-26 murine colorectal cells was confirmed to be more efficient than MGO. This cellular uptake could be inhibited by pre-incubation with CET, which confirmed the receptor-mediated endocytosis of MGO-PEG-CET. Magnetic targeted killing of CT-26 was demonstrated in vitro through magnetic guidance of MGO-PEG-CET/DOX, while the photothermal effect could be confirmed in vivo and in vitro after exposure of MGO-PEG-CET to near-infrared (NIR) laser light. In addition, the biocompatibility tests indicated MGO-PEG-CET showed no cytotoxicity toward fibroblasts and elicited minimum hemolysis. In vitro cytotoxicity tests showed the half maximal inhibitory concentration (IC50) value of MGO-PEG-CET/DOX toward CT-26 cells was 1.48 µg/mL, which was lower than that of MGO-PEG/DOX (2.64 µg/mL). The IC50 value could be further reduced to 1.17 µg/mL after combining with photothermal therapy by NIR laser light exposure. Using subcutaneously implanted CT-26 cells in BALB/c mice, in vivo anti-tumor studies indicated the relative tumor volumes at day 14 were 12.1 for control (normal saline), 10.1 for DOX, 9.5 for MGO-PEG-CET/DOX, 5.8 for MGO-PEG-CET/DOX + magnet, and 0.42 for MGO-PEG-CET/DOX + magnet + laser. Therefore, the dual targeting MGO-PEG-CET/DOX could be suggested as an effective drug delivery system for anticancer therapy, which showed a 29-fold increase in therapeutic efficacy compared with control by combining chemotherapy with photothermal therapy. View Full-Text
Keywords: graphene oxide; magnetic nanoparticles; doxorubicin; cetuximab; photothermal therapy graphene oxide; magnetic nanoparticles; doxorubicin; cetuximab; photothermal therapy
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MDPI and ACS Style

Lu, Y.-J.; Lin, P.-Y.; Huang, P.-H.; Kuo, C.-Y.; Shalumon, K.; Chen, M.-Y.; Chen, J.-P. Magnetic Graphene Oxide for Dual Targeted Delivery of Doxorubicin and Photothermal Therapy. Nanomaterials 2018, 8, 193.

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