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Graphene Nanoflake Antibody Conjugates for Multimodal Imaging of Tumors


Lamb, Jennifer; Šimaitis, Joris; Halukeerthi, Siriney O; Salzmann, Christoph G; Holland, Jason P (2021). Graphene Nanoflake Antibody Conjugates for Multimodal Imaging of Tumors. Advanced NanoBiomed Research, 1(9):2100009.

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.

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Department of Chemistry
Dewey Decimal Classification:540 Chemistry
Language:English
Date:1 September 2021
Deposited On:21 Jan 2022 06:10
Last Modified:27 May 2024 01:50
Publisher:Wiley Open Access
ISSN:2699-9307
OA Status:Gold
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1002/anbr.202100009
Project Information:
  • : FunderSNSF
  • : Grant IDPP00P2_163683
  • : Project TitleAdvanced radiochemical methods for multi-modal imaging with nanomedicines
  • : FunderSNSF
  • : Grant IDPP00P2_190093
  • : Project TitleRadiochemistry in a Flash: Advanced methods for the synthesis of multi-modal imaging agents
  • : FunderKrebsliga
  • : Grant IDKFS-4257-08-2017
  • : Project Title
  • : FunderH2020
  • : Grant ID676904
  • : Project TitleDeveloping multi-modality nanomedicines for targeted annotation of oncogenic signaling pathways
  • Content: Published Version
  • Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)