Protein‐Triggered Reassembly of Quinocyanine Nanosheets for Intraoperative NIR‐II Cholangiography

Y Yutao Zhang (Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering, Feringa Nobel Prize Scientist Joint Research Center, Institute of Fine Chemicals, Frontiers Science Center for Materiobiology and Dynamic Chemistry, School of Chemistry and Molecular Engineering, State Key Laboratory of Bioreactor Engineering, State Key Laboratory of Green Chemical Engineering and Industrial Catalysis, Center of Photosensitive Chemicals Engineering) M Menglan Wu (Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering Shanghai Key Laboratory of Functional Materials Chemistry Feringa Nobel Prize Scientist Joint Research Center Institute of Fine Chemicals Frontiers Science Center for Materiobiology and Dynamic Chemistry School of Chemistry and Molecular Engineering East China University of Science and Technology Shanghai 200237 China) W Wennan Li (Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering Shanghai Key Laboratory of Functional Materials Chemistry Feringa Nobel Prize Scientist Joint Research Center Institute of Fine Chemicals Frontiers Science Center for Materiobiology and Dynamic Chemistry School of Chemistry and Molecular Engineering East China University of Science and Technology Shanghai 200237 China) Z Zhiyong Liu (Center for Water Resources and Environment, School of Civil Engineering, Sun Yat-sen University) C Caiqi Liu (Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering Shanghai Key Laboratory of Functional Materials Chemistry Feringa Nobel Prize Scientist Joint Research Center Institute of Fine Chemicals Frontiers Science Center for Materiobiology and Dynamic Chemistry School of Chemistry and Molecular Engineering East China University of Science and Technology Shanghai 200237 China) Y Yue Wu (Genomic Analysis Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA.) C Chenxu Yan (Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering, Feringa Nobel Prize Scientist Joint Research Center, Institute of Fine Chemicals, Frontiers Science Center for Materiobiology and Dynamic Chemistry, School of Chemistry and Molecular Engineering, State Key Laboratory of Bioreactor Engineering, State Key Laboratory of Green Chemical Engineering and Industrial Catalysis, Center of Photosensitive Chemicals Engineering) Y Yisheng Xu (State Key Laboratory of Green Chemical Engineering and Industrial Catalysis State Key Laboratory of Chemical Engineering School of Chemical Engineering East China University of Science and Technology Shanghai 200237 China) W Wei‐Hong Zhu (Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering Shanghai Key Laboratory of Functional Materials Chemistry Feringa Nobel Prize Scientist Joint Research Center Institute of Fine Chemicals Frontiers Science Center For Materiobiology and Dynamic Chemistry School of Chemistry and Molecular Engineering East China University of Science and Technology Shanghai China) Z Zhiqian Guo (Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering, Feringa Nobel Prize Scientist Joint Research Center, Institute of Fine Chemicals, Frontiers Science Center for Materiobiology and Dynamic Chemistry, School of Chemistry and Molecular Engineering, State Key Laboratory of Bioreactor Engineering, State Key Laboratory of Green Chemical Engineering and Industrial Catalysis, Center of Photosensitive Chemicals Engineering)

Abstract

Abstract Intraoperative near‐infrared II (NIR‐II) fluorescence imaging offers high‐contrast, real‐time visualization during surgery, yet the development of activatable probes remains a formidable challenge because most tissue‐specific biomarkers, such as receptor proteins, are chemically inert intrinsic. Here, we present a protein‐triggered reassembly strategy in which planar NIR‐II dyes pre‐assemble into π–π stacked aggregates with quenched fluorescence that reorganize into highly emissive dye‐protein complexes upon target binding, thereby achieving activatable intraoperative imaging. Compared with indocyanine green (ICG), a clinically approved “always‐on” cholangiography agent, quinocyanine green (QCG) was developed as a bile specifical activated NIR‐II probe through stepwise molecular engineering. Native PAGE, protein sequencing, and TEM analyses all revealed that a hemoglobin subunit in bile drives the transformation of the initial QCG nanosheets into uniform homogeneous spherical protein‐dye complexes, yielding a remarkable 310‐fold fluorescence enhancement at 1011 nm. Taking such advantage, for the first time, we have clearly and directly visualized intrahepatic bile duct in vivo. Moreover, QCG afforded high‐contrast, precise intraoperative cholangiography, allowing detailed biliary tree mapping, stricture identification, bile leakage detection, and dual‐color hepatobiliary imaging. This in situ reassembly strategy establishes a generalizable molecular design principle for activatable NIR‐II probes and expands the toolbox for precision fluorescence‐guided surgery.

Article Details

Volume / Issue Vol. 65, Issue 5
Published January 28, 2026
ISSN 1433-7851
Publisher Wiley

Journal Info

Angewandte Chemie International Edition

Wiley

ISSN: 1433-7851 Physical Sciences

Authors (10)

Y

Yutao Zhang

Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering, Feringa Nobel Prize Scientist Joint Research Center, Institute of Fine Chemicals, Frontiers Science Center for Materiobiology and Dynamic Chemistry, School of Chemistry and Molecular Engineering, State Key Laboratory of Bioreactor Engineering, State Key Laboratory of Green Chemical Engineering and Industrial Catalysis, Center of Photosensitive Chemicals Engineering

M

Menglan Wu

Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering Shanghai Key Laboratory of Functional Materials Chemistry Feringa Nobel Prize Scientist Joint Research Center Institute of Fine Chemicals Frontiers Science Center for Materiobiology and Dynamic Chemistry School of Chemistry and Molecular Engineering East China University of Science and Technology Shanghai 200237 China

W

Wennan Li

Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering Shanghai Key Laboratory of Functional Materials Chemistry Feringa Nobel Prize Scientist Joint Research Center Institute of Fine Chemicals Frontiers Science Center for Materiobiology and Dynamic Chemistry School of Chemistry and Molecular Engineering East China University of Science and Technology Shanghai 200237 China

Z

Zhiyong Liu

Center for Water Resources and Environment, School of Civil Engineering, Sun Yat-sen University

C

Caiqi Liu

Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering Shanghai Key Laboratory of Functional Materials Chemistry Feringa Nobel Prize Scientist Joint Research Center Institute of Fine Chemicals Frontiers Science Center for Materiobiology and Dynamic Chemistry School of Chemistry and Molecular Engineering East China University of Science and Technology Shanghai 200237 China

Y

Yue Wu

Genomic Analysis Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA.

C

Chenxu Yan

Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering, Feringa Nobel Prize Scientist Joint Research Center, Institute of Fine Chemicals, Frontiers Science Center for Materiobiology and Dynamic Chemistry, School of Chemistry and Molecular Engineering, State Key Laboratory of Bioreactor Engineering, State Key Laboratory of Green Chemical Engineering and Industrial Catalysis, Center of Photosensitive Chemicals Engineering

Y

Yisheng Xu

State Key Laboratory of Green Chemical Engineering and Industrial Catalysis State Key Laboratory of Chemical Engineering School of Chemical Engineering East China University of Science and Technology Shanghai 200237 China

W

Wei‐Hong Zhu

Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering Shanghai Key Laboratory of Functional Materials Chemistry Feringa Nobel Prize Scientist Joint Research Center Institute of Fine Chemicals Frontiers Science Center For Materiobiology and Dynamic Chemistry School of Chemistry and Molecular Engineering East China University of Science and Technology Shanghai China

Z

Zhiqian Guo

Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering, Feringa Nobel Prize Scientist Joint Research Center, Institute of Fine Chemicals, Frontiers Science Center for Materiobiology and Dynamic Chemistry, School of Chemistry and Molecular Engineering, State Key Laboratory of Bioreactor Engineering, State Key Laboratory of Green Chemical Engineering and Industrial Catalysis, Center of Photosensitive Chemicals Engineering