Enzyme-Mediated In Situ Self-Assembly Promotes In Vivo Bioorthogonal Reaction for Pretargeted Multimodality Imaging

Yuxuan Hu; Junya Zhang; Yinxing Miao; Xidan Wen; Jian Wang; Yidan Sun; Yinfei Chen; Jianguo Lin; Ling Qiu; Kai Guo; Hong Yuan Chen; Deju Ye

doi:10.1002/anie.202103307

Enzyme-Mediated In Situ Self-Assembly Promotes In Vivo Bioorthogonal Reaction for Pretargeted Multimodality Imaging

Yuxuan Hu, Junya Zhang, Yinxing Miao, Xidan Wen, Jian Wang, Yidan Sun, Yinfei Chen, Jianguo Lin, Ling Qiu, Kai Guo, Hong Yuan Chen, Deju Ye

COLLEGE OF BIOTECHNOLOGY AND PHARMACEUTICAL ENGINEERING

Research output: Contribution to journal › Article › peer-review

79 Scopus citations

Abstract

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 (⁶⁸Ga) 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.

Original language	English
Pages (from-to)	18082-18093
Number of pages	12
Journal	Angewandte Chemie - International Edition
Volume	60
Issue number	33
DOIs	https://doi.org/10.1002/anie.202103307
State	Published - 9 Aug 2021

Keywords

bioorthogonal reactions
in vivo imaging
mulitmodality
pretargeting
self-assembly

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title = "Enzyme-Mediated In Situ Self-Assembly Promotes In Vivo Bioorthogonal Reaction for Pretargeted Multimodality Imaging",

abstract = "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 (68Ga) 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.",

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author = "Yuxuan Hu and Junya Zhang and Yinxing Miao and Xidan Wen and Jian Wang and Yidan Sun and Yinfei Chen and Jianguo Lin and Ling Qiu and Kai Guo and Chen, {Hong Yuan} and Deju Ye",

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AU - Hu, Yuxuan

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AU - Miao, Yinxing

AU - Wen, Xidan

AU - Wang, Jian

AU - Sun, Yidan

AU - Chen, Yinfei

AU - Lin, Jianguo

AU - Qiu, Ling

AU - Guo, Kai

AU - Chen, Hong Yuan

AU - Ye, Deju

PY - 2021/8/9

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AB - 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 (68Ga) 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.

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Enzyme-Mediated In Situ Self-Assembly Promotes In Vivo Bioorthogonal Reaction for Pretargeted Multimodality Imaging

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