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Asymmetric rotaxanes as dual-modality supramolecular imaging agents for targeting cancer biomarkers


d’Orchymont, Faustine; Holland, Jason P (2023). Asymmetric rotaxanes as dual-modality supramolecular imaging agents for targeting cancer biomarkers. Communications Chemistry, 6(1):107.

Abstract

Dual-modality imaging agents featuring both a radioactive complex for positron emission tomography (PET) and a fluorophore for optical fluorescence imaging (OFI) are crucial tools for reinforcing clinical diagnosis and intraoperative surgeries. We report the synthesis and characterisation of bimodal mechanically interlocked rotaxane-based imaging agents, constructed via the cucurbit[6]uril CB[6]-mediated alkyne-azide ‘click’ reaction. Two synthetic routes involving four- or six-component reactions are developed to access asymmetric rotaxanes. Furthermore, by using this rapid and versatile approach, a peptide-based rotaxane targeted toward the clinical prostate cancer biomarker, prostate-specific membrane antigen (PSMA), and bearing a 68Ga-radiometal ion complex for positron emission tomography and fluorescein as an optically active imaging agent, was synthesised. The chemical and radiochemical stability, and the cellular uptake profile of the radiolabelled and fluorescent rotaxane was evaluated in vitro where the experimental data demonstrate the viability of using an asymmetric rotaxane platform to produce dual-modality imaging agents that specifically target prostate cancer cells.

Abstract

Dual-modality imaging agents featuring both a radioactive complex for positron emission tomography (PET) and a fluorophore for optical fluorescence imaging (OFI) are crucial tools for reinforcing clinical diagnosis and intraoperative surgeries. We report the synthesis and characterisation of bimodal mechanically interlocked rotaxane-based imaging agents, constructed via the cucurbit[6]uril CB[6]-mediated alkyne-azide ‘click’ reaction. Two synthetic routes involving four- or six-component reactions are developed to access asymmetric rotaxanes. Furthermore, by using this rapid and versatile approach, a peptide-based rotaxane targeted toward the clinical prostate cancer biomarker, prostate-specific membrane antigen (PSMA), and bearing a 68Ga-radiometal ion complex for positron emission tomography and fluorescein as an optically active imaging agent, was synthesised. The chemical and radiochemical stability, and the cellular uptake profile of the radiolabelled and fluorescent rotaxane was evaluated in vitro where the experimental data demonstrate the viability of using an asymmetric rotaxane platform to produce dual-modality imaging agents that specifically target prostate cancer cells.

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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 > General Chemistry
Physical Sciences > Environmental Chemistry
Life Sciences > Biochemistry
Physical Sciences > Materials Chemistry
Uncontrolled Keywords:Materials Chemistry, Biochemistry, Environmental Chemistry, General Chemistry
Language:English
Date:1 June 2023
Deposited On:19 Feb 2024 15:01
Last Modified:30 Jun 2024 01:37
Publisher:Nature Publishing Group
ISSN:2399-3669
OA Status:Gold
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1038/s42004-023-00906-5
PubMed ID:37264077
  • Content: Published Version
  • Language: English
  • Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)