Review
Multifunctional carbon nanomaterial hybrids for magnetic manipulation and targeting

https://doi.org/10.1016/j.bbrc.2015.06.131Get rights and content

Highlights

  • Carbon nanomaterial/magnetic nanoparticle-based hybrids in the biomedical domain.

  • Applications in magnetic targeting and magnetic manipulation of cells.

  • Capacity of carbon nanomaterial/magnetic nanoparticle hybrids to capture and separate cells.

  • Implementation into devices for molecular delivery or extraction, and cellular probing.

Abstract

Nanosized materials and multifunctional nanoscale platforms have attracted in the last years considerable interest in a variety of different fields including biomedicine. Carbon nanotubes and graphene are some of the most widely used carbon nanomaterials (CNMs) due to their unique morphology and structure and their characteristic physicochemical properties. Their high surface area allows efficient drug loading and bioconjugation and makes them the ideal platforms for decoration with magnetic nanoparticles (MNPs). In the biomedical area, MNPs are of particular importance due to their broad range of potential applications in drug delivery, non-invasive tumor imaging and early detection based on their optical and magnetic properties. The remarkable characteristics of CNMs and MNPs can be combined leading to CNM/MNP hybrids which offer numerous promising, desirable and strikingly advantageous properties for improved performance in comparison to the use of either material alone. In this minireview, we attempt to comprehensively report the most recent advances made with CNMs conjugated to different types of MNPs for magnetic targeting, magnetic manipulation, capture and separation of cells towards development of magnetic carbon-based devices.

Introduction

Carbon nanomaterials (CNMs) have shown great potential in biomedical applications, mainly due to their unique chemical and physical properties [1], [2], [3], [4], [5]. Carbon nanotubes (CNTs) and graphene are two of the most widely used CNMs due to their physical and chemical stability as well as their high surface area-to-weight ratio. In the field of nanomedicine, they are used as platforms for the immobilization of nanoparticles (NPs) [6], [7] and as versatile carriers for a variety of bioactive molecules [8], [9], [10]. CNMs are also endowed with characteristic optical properties, such as fluorescence and Raman scattering, making them useful for sensing applications and a variety of imaging modalities such as magnetic resonance, near-infrared fluorescence, photoacoustic tomography, photothermal and Raman imaging [4], [5], [11], [12], [13].

Magnetic nanoparticles with appropriate physicochemically tailored surface properties, colloidal stability and biological behavior have been used in drug delivery, hyperthermia, magnetic resonance imaging (MRI), biosensing, biochemical separations and bioanalysis [14], [15], [16], [17]. The combination of CNMs and different types of MNPs has recently attracted interest in biomedical applications [18], [19], [20], [21]. In particular, CNM/MNP hybrids exhibit advantageous and often synergistic properties arising from their combination and molecular interactions [22], [23]. For instance, in sensing applications, the association of NPs with graphene renders greater catalytic and conducting properties, enhancing their sensitivity and selectivity in comparison to graphene- or NP-based sensors alone [24]. Endowing CNMs with magnetic properties thanks to the association with MNPs is opening many opportunities for future biomedical applications.

In this minireview, we describe the association of CNMs, mainly CNTs and graphene, and MNPs for various biological applications. Specifically, we will focus on CNM/NP hybrids for magnetic targeting in multifunctional drug delivery and imaging, for biosensing, for magnetic molecular extraction, magnetic manipulation, capture and release of cells. We will also discuss the ability of CNT/NP hybrid for magnetic manipulation and fabrication of biomedical devices.

Section snippets

Magnetic targeting

The combination of CNMs and NPs has led to the generation of novel systems that are finding a wide range of applications in biomedicine due to their versatile magnetic properties. Advanced multifunctional magnetic CNM-based vectors bearing fluorescent moieties [e.g. fluorescein isothiocyanate (FITC)], proteins (e.g. transferrin), targeting ligands [e.g. folic acid (FA)] or therapeutic drugs [e.g. doxorubicin (DOX)] have been used not only in targeted therapies, but also in imaging and

Magnetic manipulation of cells

In the field of cell-based cancer therapy, nanosystems made of magnetic CNTs have been considered promising tools as they allow to combine their high cellular uptake efficiency with magnetic responsiveness. Based on the metallic impurities entrapped into CNTs during the synthesis process and their interactions with cells, CNTs have been used for cellular manipulation. Functionalized MWCNT-bound cells proved to cause progressive cell displacement towards the most intensive magnetic field zones

Capture and separation of cells

Numerous studies have reported the use of magnetic CNMs for magnetic separation and purification of low-abundant biomolecules, including proteins [53], [54], [55], [56], antigens [57], phosphopeptides [58], [59], and DNA, from complex biological samples [60].

The magnetic properties of CNM/NP hybrids have also been exploited to capture and separate cells from a pool of cells or from blood. Fe-filled MWCNTs conjugated to a monoclonal antibody (Cetuximab) that selectively binds the epidermal

Magnetic carbon nanotube-based devices for molecular delivery or extraction, and cellular probing

Vertically aligned CNTs with ferromagnetic catalyst nickel particles embedded in their tips have been used to transfect genetic materials into cells [79]. DNA plasmids (pDNA) encoding for enhanced green fluorescent protein (EGFP) sequence were immobilized on the nanotube surface. The CNTs penetrated the cell membranes driven by a magnetic field. This nanotube spearing effect allowed efficient delivery of pDNA in hard-to-transfect cells such as B cells and primary neurons with high viability.

Perspectives

Carbon-based nanomaterials are becoming important elements for the innovation in the field of nanobiotechnology and nanomedicine. The recent advances have been possible thanks to the development of multifunctional biocompatible systems. As illustrated by the examples described in the above sections, intense efforts have been devoted to the design of hybrids between CNMs and NPs endowed of magnetic properties. The combination of these two types of nanomaterials is opening the doors to the new

Acknowledgments

This work was supported by the Centre National de la Recherche Scientifique (CNRS), by the Agence Nationale de la Recherche (ANR) through the LabEx project Chemistry of Complex Systems (ANR-10-LABX-0026_CSC), and by the International Center for Frontier Research in Chemistry (icFRC). The authors gratefully acknowledge financial support from EU FP7-ICT-2013-FET-F GRAPHENE Flagship project (no. 604391).

References (87)

  • Y.J. Lu et al.

    Dual targeted delivery of doxorubicin to cancer cells using folate-conjugated magnetic multi-walled carbon nanotubes

    Colloids Surf. B Biointerfaces

    (2012)
  • Y. Wang et al.

    MRI-visualized, dual-targeting, combined tumor therapy using magnetic graphene-based mesoporous silica

    Small

    (2014)
  • X. Shi et al.

    Graphene-based magnetic plasmonic nanocomposite for dual bioimaging and photothermal therapy

    Biomaterials

    (2013)
  • F. Yang et al.

    Magnetic lymphatic targeting drug delivery system using carbon nanotubes

    Med. Hypotheses

    (2008)
  • F. Yang et al.

    Magnetic functionalised carbon nanotubes as drug vehicles for cancer lymph node metastasis treatment

    Eur. J. Cancer

    (2011)
  • H. Wang et al.

    Optically encoded nanoprobes using single walled carbon nanotube as the building scaffold for magnetic field guided cell imaging

    Talanta

    (2014)
  • S. Park et al.

    Manipulation of NIH3T3 cells with functionalized single-walled carbon nanotubes under a magnetic field

    Mater. Lett.

    (2012)
  • X. Ding et al.

    Preparation of magnetic chitosan and graphene oxide-functional guanidinium ionic liquid composite for the solid-phase extraction of protein

    Anal. Chim. Acta

    (2015)
  • T.R. Fadel et al.

    Immunotherapy applications of carbon nanotubes: from design to safe applications

    Trends Biotechnol.

    (2014)
  • D.A. Jasim et al.

    Tissue distribution and urinary excretion of intravenously administered chemically functionalized graphene oxide sheets

    Chem. Sci.

    (2015)
  • K.V. Krishna et al.

    Graphene-based nanomaterials for nanobiotechnology and biomedical applications

    Nanomed. (Lond)

    (2013)
  • G. Hong et al.

    Carbon nanomaterials for biological imaging and nanomedicinal therapy

    Chem. Rev.

    (2015)
  • D. Pantarotto et al.

    Functionalized carbon nanotubes for plasmid DNA gene delivery

    Angew. Chem. Int. Ed.

    (2004)
  • K. Kostarelos et al.

    Promises, facts and challenges for carbon nanotubes in imaging and therapeutics

    Nat. Nanotechnol.

    (2009)
  • C. Chung et al.

    Biomedical applications of graphene and graphene oxide

    Acc. Chem. Res.

    (2013)
  • N. Karousis et al.

    Current progress on the chemical modification of carbon nanotubes

    Chem. Rev.

    (2010)
  • S. Bai et al.

    Graphene–inorganic nanocomposites

    RSC Adv.

    (2012)
  • C. Ménard-Moyon et al.

    The alluring potential of functionalized carbon nanotubes in drug discovery

    Expert Opin. Drug Discov.

    (2010)
  • A.H. Hung et al.

    Graphene oxide enhances cellular delivery of hydrophilic small molecules by co-incubation

    ACS Nano

    (2014)
  • S. Laurent et al.

    Magnetic iron oxide nanoparticles: synthesis, stabilization, vectorization, physicochemical characterizations, and biological applications

    Chem. Rev.

    (2008)
  • L.H. Reddy et al.

    Magnetic nanoparticles: design and characterization, toxicity and biocompatibility, pharmaceutical and biomedical applications

    Chem. Rev.

    (2012)
  • S.Y. Madani et al.

    Conjugation of quantum dots on carbon nanotubes for medical diagnosis and treatment

    Int. J. Nanomed.

    (2013)
  • V. Georgakilas et al.

    Functionalization of graphene: covalent and non-covalent approaches, derivatives and applications

    Chem. Rev.

    (2012)
  • K. Yang et al.

    Nano-graphene in biomedicine: theranostic applications

    Chem. Soc. Rev.

    (2013)
  • R. Villalonga et al.

    Decorating carbon nanotubes with polyethylene glycol-coated magnetic nanoparticles for implementing highly sensitive enzyme biosensors

    J. Mater. Chem.

    (2011)
  • J. Guerra et al.

    Hybrid materials based on Pd nanoparticles on carbon nanostructures for environmentally benign C–C coupling chemistry

    Nanoscale

    (2010)
  • X. Yang et al.

    Superparamagnetic graphene oxide–Fe3O4 nanoparticles hybrid for controlled targeted drug carriers

    J. Mater. Chem.

    (2009)
  • X. Yang et al.

    Multi-functionalized graphene oxide based anticancer drug-carrier with dual-targeting function and pH-sensitivity

    J. Mater. Chem.

    (2011)
  • X. Fan et al.

    Magnetic Fe3O4-graphene composites as targeted drug nanocarriers for pH-activated release

    Nanoscale

    (2013)
  • S. a. Chechetka et al.

    Multifunctional carbon nanohorn complexes for cancer treatment

    Chem. Asian J

    (2015)
  • X. Ma et al.

    A functionalized graphene oxide-iron oxide nanocomposite for magnetically targeted drug delivery, photothermal therapy, and magnetic resonance imaging

    Nano Res.

    (2012)
  • M.L. Chen et al.

    Quantum dots conjugated with Fe3O4-filled carbon nanotubes for cancer-targeted imaging and magnetically guided drug delivery

    Langmuir

    (2012)
  • O. Akhavan et al.

    Zinc ferrite spinel-graphene in magneto-photothermal therapy of cancer

    J. Mater. Chem. B

    (2014)
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