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Supramolecular Rotaxane-Based Multi-Modal Probes for Cancer Biomarker Imaging


d'Orchymont, Faustine; Holland, Jason P (2022). Supramolecular Rotaxane-Based Multi-Modal Probes for Cancer Biomarker Imaging. Angewandte Chemie Internationale Edition, 61:e202204072.

Abstract

Mechanically interlocked molecules present opportunities to construct therapeutic drugs and diagnostic imaging agents but harnessing supramolecular chemistry to make biologically active probes in water is a challenge. Here, we describe a rotaxane-based approach to synthesise radiolabelled proteins and peptides for molecular imaging of cancer biomarkers in vivo. Host–guest chemistry using β-cyclodextrin- and cucurbit[6]uril-catalysed cooperative capture synthesis produced gallium-68 or zirconium-89 radiolabelled metallo[4]rotaxanes. Photochemical conjugation to trastuzumab led to a viable positron emission tomography (PET) radiotracer. The rotaxane architecture can be tuned to accommodate different radiometal ion complexes, other protein- or peptide-based drugs, and fluorophores for optical detection. This technology provides a platform to explore how mechanical bonding can improve drug delivery, enhance tumour specificity, control radiotracer pharmacokinetics, and reduce dosimetry.

Abstract

Mechanically interlocked molecules present opportunities to construct therapeutic drugs and diagnostic imaging agents but harnessing supramolecular chemistry to make biologically active probes in water is a challenge. Here, we describe a rotaxane-based approach to synthesise radiolabelled proteins and peptides for molecular imaging of cancer biomarkers in vivo. Host–guest chemistry using β-cyclodextrin- and cucurbit[6]uril-catalysed cooperative capture synthesis produced gallium-68 or zirconium-89 radiolabelled metallo[4]rotaxanes. Photochemical conjugation to trastuzumab led to a viable positron emission tomography (PET) radiotracer. The rotaxane architecture can be tuned to accommodate different radiometal ion complexes, other protein- or peptide-based drugs, and fluorophores for optical detection. This technology provides a platform to explore how mechanical bonding can improve drug delivery, enhance tumour specificity, control radiotracer pharmacokinetics, and reduce dosimetry.

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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
Scopus Subject Areas:Physical Sciences > Catalysis
Physical Sciences > General Chemistry
Uncontrolled Keywords:General Chemistry, Catalysis
Language:English
Date:18 July 2022
Deposited On:05 Jan 2023 09:46
Last Modified:29 Mar 2024 02:37
Publisher:Wiley-VCH Verlag
ISSN:1433-7851
OA Status:Hybrid
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1002/anie.202204072
Project Information:
  • : FunderSwiss National Science Foundation
  • : Grant IDPP00P2_163683
  • : Project Title
  • : FunderSwiss National Science Foundation
  • : Grant IDPP00P2_190093
  • : Project Title
  • : FunderSwiss Government Excellence Scholarship
  • : Grant ID2017.0043
  • : Project Title
  • Content: Published Version
  • Licence: Creative Commons: Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
  • Content: Accepted Version