Difluoroboronated tetrazine probes for rapid bioorthogonal fluorescence activation, no-wash STED imaging, and triggered drug release

Xiaomei Zhu; Jie Zhang; Haoxing Geng; Kai Wang; Yue Li; Xiuxiu Yang; Heng Shi; Junjie Tai; Xueyuan Yan; Yunfang Yang; Hongyan Sun; Qing Zhu

doi:10.1126/sciadv.adw1098

Difluoroboronated tetrazine probes for rapid bioorthogonal fluorescence activation, no-wash STED imaging, and triggered drug release

Xiaomei Zhu (Co-first Author)
, Jie Zhang (Co-first Author)
, Haoxing Geng (Co-first Author)
, Kai Wang
, Yue Li
, Xiuxiu Yang
, Heng Shi
, Junjie Tai
, Xueyuan Yan
, Yunfang Yang^*
, Hongyan Sun^*
, Qing Zhu^*

^*Corresponding author for this work

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

7 Citations (Scopus)

4 Downloads (CityUHK Scholars)

Abstract

A unique class of bioorthogonal fluorogenic probes, based on difluoroboronated tetrazine (Tz-BFs), has been developed. These probes are the smallest tetrazine-based fluorescent structures and exhibit a high fluorescence turn-on ratio (up to 582-fold) following the inverse electron-demand Diels-Alder reaction. By engineering π-conjugated systems and using push-pull groups, their fluorescence emission can be tuned across blue to yellow (440 to 570 nanometers). They offer no-wash fluorogenic behavior, excellent cell permeability, rapid reaction kinetics, and high photostability, ideal for real-time biomolecule tracking, suborganelle bioorthogonal imaging, and metabolic labeling. In addition, they enable stimulated emission depletion (STED) microscopy for subdiffraction resolution imaging and have click-to-release functionality for simultaneous fluorescence activation and therapeutic agent release, such as TCO (trans-cyclooctene)–DOX (doxorubicin). These probes provide broad potential for advanced imaging and drug delivery applications. Copyright © 2025 The Authors, some rights reserved.

Original language	English
Article number	eadw1098
Journal	Science Advances
Volume	11
Issue number	33
Online published	15 Aug 2025
DOIs	https://doi.org/10.1126/sciadv.adw1098
Publication status	Published - Aug 2025

Funding

We are grateful to the National Natural Science Foundation of China (nos. 22177103 to Q.Z. and 21978272 to Y.Y.), Research Grants Council of Hong Kong (grant nos. 11312422 and 11302224 to H.S.), and the Fundamental Research Funds for the Provincial Universities of Zhejiang (RF-C2022006 to Y.Y.).

Publisher's Copyright Statement

This full text is made available under CC-BY-NC 4.0. https://creativecommons.org/licenses/by-nc/4.0/

RGC Funding Information

RGC-funded

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@article{c8bde07355c24ca7961eaf7eb02637f5,

title = "Difluoroboronated tetrazine probes for rapid bioorthogonal fluorescence activation, no-wash STED imaging, and triggered drug release",

abstract = "A unique class of bioorthogonal fluorogenic probes, based on difluoroboronated tetrazine (Tz-BFs), has been developed. These probes are the smallest tetrazine-based fluorescent structures and exhibit a high fluorescence turn-on ratio (up to 582-fold) following the inverse electron-demand Diels-Alder reaction. By engineering π-conjugated systems and using push-pull groups, their fluorescence emission can be tuned across blue to yellow (440 to 570 nanometers). They offer no-wash fluorogenic behavior, excellent cell permeability, rapid reaction kinetics, and high photostability, ideal for real-time biomolecule tracking, suborganelle bioorthogonal imaging, and metabolic labeling. In addition, they enable stimulated emission depletion (STED) microscopy for subdiffraction resolution imaging and have click-to-release functionality for simultaneous fluorescence activation and therapeutic agent release, such as TCO (trans-cyclooctene)–DOX (doxorubicin). These probes provide broad potential for advanced imaging and drug delivery applications. Copyright {\textcopyright} 2025 The Authors, some rights reserved.",

author = "Xiaomei Zhu and Jie Zhang and Haoxing Geng and Kai Wang and Yue Li and Xiuxiu Yang and Heng Shi and Junjie Tai and Xueyuan Yan and Yunfang Yang and Hongyan Sun and Qing Zhu",

year = "2025",

month = aug,

doi = "10.1126/sciadv.adw1098",

language = "English",

volume = "11",

journal = "Science Advances",

issn = "2375-2548",

publisher = "American Association for the Advancement of Science",

number = "33",

}

Difluoroboronated tetrazine probes for rapid bioorthogonal fluorescence activation, no-wash STED imaging, and triggered drug release. / Zhu, Xiaomei (Co-first Author); Zhang, Jie (Co-first Author); Geng, Haoxing (Co-first Author) et al.
In: Science Advances, Vol. 11, No. 33, eadw1098, 08.2025.

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

TY - JOUR

T1 - Difluoroboronated tetrazine probes for rapid bioorthogonal fluorescence activation, no-wash STED imaging, and triggered drug release

AU - Zhu, Xiaomei

AU - Zhang, Jie

AU - Geng, Haoxing

AU - Wang, Kai

AU - Li, Yue

AU - Yang, Xiuxiu

AU - Shi, Heng

AU - Tai, Junjie

AU - Yan, Xueyuan

AU - Yang, Yunfang

AU - Sun, Hongyan

AU - Zhu, Qing

PY - 2025/8

Y1 - 2025/8

N2 - A unique class of bioorthogonal fluorogenic probes, based on difluoroboronated tetrazine (Tz-BFs), has been developed. These probes are the smallest tetrazine-based fluorescent structures and exhibit a high fluorescence turn-on ratio (up to 582-fold) following the inverse electron-demand Diels-Alder reaction. By engineering π-conjugated systems and using push-pull groups, their fluorescence emission can be tuned across blue to yellow (440 to 570 nanometers). They offer no-wash fluorogenic behavior, excellent cell permeability, rapid reaction kinetics, and high photostability, ideal for real-time biomolecule tracking, suborganelle bioorthogonal imaging, and metabolic labeling. In addition, they enable stimulated emission depletion (STED) microscopy for subdiffraction resolution imaging and have click-to-release functionality for simultaneous fluorescence activation and therapeutic agent release, such as TCO (trans-cyclooctene)–DOX (doxorubicin). These probes provide broad potential for advanced imaging and drug delivery applications. Copyright © 2025 The Authors, some rights reserved.

AB - A unique class of bioorthogonal fluorogenic probes, based on difluoroboronated tetrazine (Tz-BFs), has been developed. These probes are the smallest tetrazine-based fluorescent structures and exhibit a high fluorescence turn-on ratio (up to 582-fold) following the inverse electron-demand Diels-Alder reaction. By engineering π-conjugated systems and using push-pull groups, their fluorescence emission can be tuned across blue to yellow (440 to 570 nanometers). They offer no-wash fluorogenic behavior, excellent cell permeability, rapid reaction kinetics, and high photostability, ideal for real-time biomolecule tracking, suborganelle bioorthogonal imaging, and metabolic labeling. In addition, they enable stimulated emission depletion (STED) microscopy for subdiffraction resolution imaging and have click-to-release functionality for simultaneous fluorescence activation and therapeutic agent release, such as TCO (trans-cyclooctene)–DOX (doxorubicin). These probes provide broad potential for advanced imaging and drug delivery applications. Copyright © 2025 The Authors, some rights reserved.

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DO - 10.1126/sciadv.adw1098

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C2 - 40815648

SN - 2375-2548

VL - 11

JO - Science Advances

JF - Science Advances

IS - 33

M1 - eadw1098

ER -

Difluoroboronated tetrazine probes for rapid bioorthogonal fluorescence activation, no-wash STED imaging, and triggered drug release

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GRF: Chemical Tools for Investigating Lysine Demethylases in Chemoresistance of Triple-Negative Breast Cancer

GRF: Developing Novel Photostable Fluorescent Probes for Detecting Granzyme and Evaluating Natural Killer Cell Activity

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Difluoroboronated tetrazine probes for rapid bioorthogonal fluorescence activation, no-wash STED imaging, and triggered drug release

Abstract

Funding

Publisher's Copyright Statement

RGC Funding Information

Access Output

Other Access Options

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Projects

GRF: Chemical Tools for Investigating Lysine Demethylases in Chemoresistance of Triple-Negative Breast Cancer

GRF: Developing Novel Photostable Fluorescent Probes for Detecting Granzyme and Evaluating Natural Killer Cell Activity

Cite this