Biochemical and Biophysical Research Communications
ReviewMultifunctional carbon nanomaterial hybrids for magnetic manipulation and targeting
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).
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