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Tetrazine Carbon Nanotubes for Pretargeted In Vivo "Click-to-Release" Bioorthogonal Tumour Imaging.

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Li, He 
Conde, João 
Guerreiro, Ana 
Bernardes, Gonçalo JL  ORCID logo  https://orcid.org/0000-0001-6594-8917

Abstract

The bioorthogonal inverse-electron-demand Diels-Alder (IEDDA) cleavage reaction between tetrazine and trans-cyclooctene (TCO) is a powerful way to control the release of bioactive agents and imaging probes. In this study, a pretargeted activation strategy using single-walled carbon nanotubes (SWCNTs) that bear tetrazines (TZ@SWCNTs) and a TCO-caged molecule was used to deliver active effector molecules. To optimize a turn-on signal by using in vivo fluorescence imaging, we developed a new fluorogenic near-infrared probe that can be activated by bioorthogonal chemistry and image tumours in mice by caging hemicyanine with TCO (tHCA). With our pretargeting strategy, we have shown selective doxorubicin prodrug activation and instantaneous fluorescence imaging in living cells. By combining a tHCA probe and a pretargeted bioorthogonal approach, real-time, non-invasive tumour visualization with a high target-to-background ratio was achieved in a xenograft mice tumour model. The combined advantages of enhanced stability, kinetics and biocompatibility, and the superior pharmacokinetics of tetrazine-functionalised SWCNTs could allow application of targeted bioorthogonal decaging approaches with minimal off-site activation of fluorophore/drug.

Description

Keywords

biorthogonal activation, carbon nanotubes, decaging, fluorogenic, targeted release, Animals, Cycloaddition Reaction, Diagnostic Imaging, Humans, Infrared Rays, MCF-7 Cells, Mice, Nanotubes, Carbon

Journal Title

Angew Chem Int Ed Engl

Conference Name

Journal ISSN

1433-7851
1521-3773

Volume Title

59

Publisher

Wiley

Rights

All rights reserved
Sponsorship
European Commission Horizon 2020 (H2020) Marie Sklodowska-Curie actions (792504)
Royal Society (URF\R\180019)