Abstract
Graphene‐based materials are promising scaffolds for use in the design of tailored‐made nanomedicines. Herein, the synthesis and characterization of a series of multifunctional carboxylated graphene nanoflakes (GNFs) conjugated to monoclonal antibodies (mAbs) for tumor‐specific binding and modulation of pharmacokinetics is presented. GNF–mAb constructs are coupled to a fluorophore (4,4‐difluoro‐4‐bora‐3a,4a‐diaza‐s‐indacene [BODIPY]) for applications in optical imaging, a paramagnetic Gd3+ complex, [GdDOTAGA(H2O)]−, and the hexadentate chelate desferrioxamine B (DFO) for radiolabeling with 89Zr4+ (t1/2 = 78.41 h) ions and applications in dual‐modality positron emission tomography/magnetic resonance imaging (PET/MRI). Experimental properties of [89Zr]GdDOTAGA–ZrDFO–GNF–trastuzumab are tested in extensive chemical, spectroscopic, radiochemical, and cellular assays in vitro, and assessment of the pharmacokinetics by PET imaging in mice bearing a human ovarian cancer model illustrates the potential of using GNF–mAbs to develop multifunctional PET/MRI probes.
Highlights
graphene nanoflakes (GNFs)–monoclonal antibodies (mAbs) constructs are coupled to a fluorophore (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene [BODIPY]) for applications in optical imaging, a paramagnetic Gd3þ complex, [GdDOTAGA(H2O)]À, and the hexadentate chelate desferrioxamine B (DFO) for radiolabeling with 89Zr4þ (t1/2 1⁄4 78.41 h) ions and applications in dual-modality positron emission tomography/magnetic resonance imaging (PET/MRI)
The experimental data acquired by using chemical, radiochemical, optical spectroscopy, cellular binding assays, and full pharmacokinetic analysis via PET imaging and biodistribution studies confirm that GNFs are a flexible platform for the future design of multimodality nanomedicines for optical imaging, PET/MRI, and tumor-specific drug delivery
Activity in the liver was not observed in images of the control construct [89Zr]GdDOTAGA–ZrDFO–GNF
Summary
The versatile properties of graphene materials such as carbon nanotubes, graphene oxide (GO), and reduced GO (rGO) nanoparticles have been harnessed to produce multimodality agents for diagnostic imaging and targeted drug delivery in cancers.[1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19]. In an early example of using graphene-based materials in nanomedicine, McDevitt et al conjugated rituximab to carbon nanotubes by using a maleimide coupling to the cysteine residues.[3].
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