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Enzyme‐Mediated In Situ Self‐Assembly Promotes In Vivo Bioorthogonal Reaction for Pretargeted Multimodality Imaging
Author(s) -
Hu Yuxuan,
Zhang Junya,
Miao Yinxing,
Wen Xidan,
Wang Jian,
Sun Yidan,
Chen Yinfei,
Lin Jianguo,
Qiu Ling,
Guo Kai,
Chen HongYuan,
Ye Deju
Publication year - 2021
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202103307
Subject(s) - bioorthogonal chemistry , tetrazine , positron emission tomography , in situ , in vivo , nuclear imaging , preclinical imaging , magnetic resonance imaging , chemistry , click chemistry , materials science , radiochemistry , nuclear medicine , combinatorial chemistry , radiology , medicine , microbiology and biotechnology , organic chemistry , biology
Pretargeted imaging has emerged as a promising approach to advance nuclear imaging of malignant tumors. Herein, we combine the enzyme‐mediated fluorogenic reaction and in situ self‐assembly with the inverse electron demand Diels–Alder (IEDDA) reaction to develop an activatable pretargeted strategy for multimodality imaging. The trans‐cyclooctene (TCO) bearing small‐molecule probe, P‐FFGd‐TCO , can be activated by alkaline phosphatase and in situ self‐assembles into nanoaggregates ( FMNPs‐TCO ) retained on the membranes, permitting to (1) amplify near‐infrared (NIR) fluorescence (FL) and magnetic resonance imaging (MRI) signals, and (2) enrich TCOs to promote IEDDA ligation. The Gallium‐68 ( 68 Ga) labeled tetrazine can readily conjugate the tumor‐retained FMNPs‐TCO to enhance radioactivity uptake in tumors. Strong NIR FL, MRI, and positron emission tomography (PET) signals are concomitantly achieved, allowing for pretargeted multimodality imaging of ALP activity in HeLa tumor‐bearing mice.