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      Multifunctional graphene oxide/iron oxide nanoparticles for magnetic targeted drug delivery dual magnetic resonance/fluorescence imaging and cancer sensing

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      PLoS ONE
      Public Library of Science

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          Abstract

          Graphene Oxide (GO) has recently attracted substantial attention in biomedical field as an effective platform for biological sensing, tissue scaffolds and in vitro fluorescence imaging. However, the targeting modality and the capability of its in vivo detection have not been explored. To enhance the functionality of GO, we combine it with superparamagnetic iron oxide nanoparticles (Fe 3O 4 NPs) serving as a biocompatible magnetic drug delivery addends and magnetic resonance contrast agent for MRI. Synthesized GO-Fe 3O 4 conjugates have an average size of 260 nm and show low cytotoxicity comparable to that of GO. Fe 3O 4 nanoparticles provide superparamagnetic properties for magnetic targeted drug delivery allowing simple manipulation by the magnetic field and magnetic resonance imaging with high r 2/r 1 relaxivity ratios of ~10.7. GO-Fe 3O 4 retains pH-sensing capabilities of GO used in this work to detect cancer versus healthy environments in vitro and exhibits fluorescence in the visible for bioimaging. As a drug delivery platform GO-Fe 3O 4 shows successful fluorescence-tracked transport of hydrophobic doxorubicin non-covalently conjugated to GO with substantial loading and 2.5-fold improved efficacy. As a result, we propose GO-Fe 3O 4 nanoparticles as a novel multifunctional magnetic targeted platform for high efficacy drug delivery traced in vitro by GO fluorescence and in vivo via MRI capable of optical cancer detection.

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          Most cited references67

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          Biomedical applications of graphene and graphene oxide.

          Graphene has unique mechanical, electronic, and optical properties, which researchers have used to develop novel electronic materials including transparent conductors and ultrafast transistors. Recently, the understanding of various chemical properties of graphene has facilitated its application in high-performance devices that generate and store energy. Graphene is now expanding its territory beyond electronic and chemical applications toward biomedical areas such as precise biosensing through graphene-quenched fluorescence, graphene-enhanced cell differentiation and growth, and graphene-assisted laser desorption/ionization for mass spectrometry. In this Account, we review recent efforts to apply graphene and graphene oxides (GO) to biomedical research and a few different approaches to prepare graphene materials designed for biomedical applications. Because of its excellent aqueous processability, amphiphilicity, surface functionalizability, surface enhanced Raman scattering (SERS), and fluorescence quenching ability, GO chemically exfoliated from oxidized graphite is considered a promising material for biological applications. In addition, the hydrophobicity and flexibility of large-area graphene synthesized by chemical vapor deposition (CVD) allow this material to play an important role in cell growth and differentiation. The lack of acceptable classification standards of graphene derivatives based on chemical and physical properties has hindered the biological application of graphene derivatives. The development of an efficient graphene-based biosensor requires stable biofunctionalization of graphene derivatives under physiological conditions with minimal loss of their unique properties. For the development graphene-based therapeutics, researchers will need to build on the standardization of graphene derivatives and study the biofunctionalization of graphene to clearly understand how cells respond to exposure to graphene derivatives. Although several challenging issues remain, initial promising results in these areas point toward significant potential for graphene derivatives in biomedical research.
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            Nanoparticle delivery of cancer drugs.

            Nanomedicine, the application of nanotechnology to medicine, enabled the development of nanoparticle therapeutic carriers. These drug carriers are passively targeted to tumors through the enhanced permeability and retention effect, so they are ideally suited for the delivery of chemotherapeutics in cancer treatment. Indeed, advances in nanomedicine have rapidly translated into clinical practice. To date, there are five clinically approved nanoparticle chemotherapeutics for cancer and many more under clinical investigation. In this review, we discuss the various nanoparticle drug delivery platforms and the important concepts involved in nanoparticle drug delivery. We also review the clinical data on the approved nanoparticle therapeutics as well as the nanotherapeutics under clinical investigation.
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              Graphene and graphene oxide: biofunctionalization and applications in biotechnology

              Graphene is the basic building block of 0D fullerene, 1D carbon nanotubes, and 3D graphite. Graphene has a unique planar structure, as well as novel electronic properties, which have attracted great interests from scientists. This review selectively analyzes current advances in the field of graphene bioapplications. In particular, the biofunctionalization of graphene for biological applications, fluorescence-resonance-energy-transfer-based biosensor development by using graphene or graphene-based nanomaterials, and the investigation of graphene or graphene-based nanomaterials for living cell studies are summarized in more detail. Future perspectives and possible challenges in this rapidly developing area are also discussed.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Formal analysisRole: Investigation
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                6 June 2019
                2019
                : 14
                : 6
                : e0217072
                Affiliations
                [001]Department of Physics & Astronomy, Texas Christian University, Fort Worth, TX, United States of America
                Consiglio Nazionale delle Ricerche, ITALY
                Author notes

                Competing Interests: The authors declare that they have no competing interests.

                Article
                PONE-D-18-33611
                10.1371/journal.pone.0217072
                6553710
                31170197
                ca6b8ed1-bd2a-437e-9f73-a4b66f5993a9
                © 2019 Gonzalez-Rodriguez et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 22 November 2018
                : 3 May 2019
                Page count
                Figures: 7, Tables: 0, Pages: 18
                Funding
                Funded by: TCU Invests in Scholarship grant.
                Award Recipient : Anton Naumov
                Funded by: Initiative for Oncology Research Grant
                Award Recipient : Anton Naumov
                This work was supported with INFOR (Initiative for Oncology Research Grant), and TCU Invests in Scholarship grant.
                Categories
                Research Article
                Medicine and Health Sciences
                Diagnostic Medicine
                Diagnostic Radiology
                Magnetic Resonance Imaging
                Research and Analysis Methods
                Imaging Techniques
                Diagnostic Radiology
                Magnetic Resonance Imaging
                Medicine and Health Sciences
                Radiology and Imaging
                Diagnostic Radiology
                Magnetic Resonance Imaging
                Medicine and Health Sciences
                Pharmaceutics
                Drug Delivery
                Research and Analysis Methods
                Imaging Techniques
                Fluorescence Imaging
                Engineering and Technology
                Nanotechnology
                Nanoparticles
                Physical Sciences
                Physics
                Electromagnetic Radiation
                Luminescence
                Fluorescence
                Medicine and Health Sciences
                Diagnostic Medicine
                Cancer Detection and Diagnosis
                Medicine and Health Sciences
                Oncology
                Cancer Detection and Diagnosis
                Physical Sciences
                Materials Science
                Materials
                Graphene
                Research and analysis methods
                Biological cultures
                Cell lines
                HeLa cells
                Research and analysis methods
                Biological cultures
                Cell cultures
                Cultured tumor cells
                HeLa cells
                Custom metadata
                All relevant data are within the manuscript and its Supporting Information files.

                Uncategorized
                Uncategorized

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