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The development of efficient contrast agents for tumor-targeted imaging remains a critical challenge in the clinic. Herein, we proposed a tumor-derived extracellular vesicle (EV)-mediated targeting approach to improve in vivo tumor imaging using ternary downconversion nanoparticles (DCNPs) with strong near infrared II (NIR-II) luminescence at 1,525 nm. The EVs were metabolically engineered with azide group, followed by in vivo labeling of DCNPs through copper-free click chemistry. By taking advantage of the homologous targeting property of tumor derived EVs, remarkable improvement in the tumor accumulation (6.5% injection dose (ID)/g) was achieved in the subcutaneous colorectal cancer model when compared to that of individual DCNPs via passive targeting (1.1% ID/g). Importantly, such bioorthogonal labeling significantly increased NIR-II luminescence signals and prolonged the retention at tumor sites. Our work demonstrates the great potential of EVs-mediated bioorthogonal approach for in vivo labeling of NIR-II optical probes, which provides a robust tool for tumor-specific imaging and targeted therapy.


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In vivo bioorthogonal labeling of rare-earth doped nanoparticles for improved NIR-II tumor imaging by extracellular vesicle-mediated targeting

Show Author's information Hui Li1,2,§Yanfeng Zhong3,§Shumin Wang1Menglei Zha4Wenxing Gu1Guoyong Liu1Bohan Wang5Zhendong Yu3( )Yu Wang5Kai Li4Yuxin Yin1Jing Mu1( )Xiaoyuan Chen2,6( )
Institute of Precision Medicine, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen 518036, China
Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and College of Design and Engineering, National University of Singapore, Singapore 119074, Singapore
Central Laboratory, Peking University Shenzhen Hospital, Shenzhen 518036, China
Department of Biomedical Engineering, Southern University of Science and Technology (SUSTech), Shenzhen 518055, China
Institute of Microscale Optoelectronics, Shenzhen University, Shenzhen 518060, China
Institute of Molecular and Cell Biology, Agency for Science, Technology, and Research (A*STAR), 61 Biopolis Drive, Proteos, Singapore 138673, Singapore

§ Hui Li and Yanfeng Zhong contributed equally to this work.

Abstract

The development of efficient contrast agents for tumor-targeted imaging remains a critical challenge in the clinic. Herein, we proposed a tumor-derived extracellular vesicle (EV)-mediated targeting approach to improve in vivo tumor imaging using ternary downconversion nanoparticles (DCNPs) with strong near infrared II (NIR-II) luminescence at 1,525 nm. The EVs were metabolically engineered with azide group, followed by in vivo labeling of DCNPs through copper-free click chemistry. By taking advantage of the homologous targeting property of tumor derived EVs, remarkable improvement in the tumor accumulation (6.5% injection dose (ID)/g) was achieved in the subcutaneous colorectal cancer model when compared to that of individual DCNPs via passive targeting (1.1% ID/g). Importantly, such bioorthogonal labeling significantly increased NIR-II luminescence signals and prolonged the retention at tumor sites. Our work demonstrates the great potential of EVs-mediated bioorthogonal approach for in vivo labeling of NIR-II optical probes, which provides a robust tool for tumor-specific imaging and targeted therapy.

Keywords: tumor imaging, extracellular vesicles, NIR-II, rare earth-doped nanoparticles, bioorthogonal labeling

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Publication history
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Acknowledgements

Publication history

Received: 22 July 2022
Revised: 01 September 2022
Accepted: 09 September 2022
Published: 23 November 2022
Issue date: February 2023

Copyright

© Tsinghua University Press 2022

Acknowledgements

Acknowledgements

This work was financially supported by the China Postdoctoral Science Foundation (No. 2022M712157), China National Postdoctoral Program for Innovative Talents (No. BX20220215), China Scientific Research Foundation of Peking University Shenzhen Hospital (No. KYQD202100X), the National Natural Science Foundation of China (No. 32101074), Shenzhen Science and Technology Innovation Committee Discipline Layout Project (No. JCYJ20170816105345191), National University of Singapore Start-up Grant (No. NUHSRO/2020/133/Startup/08), NUS School of Medicine Nanomedicine Translational Research Programme (No. NUHSRO/2021/034/TRP/09/Nanomedicine), and the National Medical Research Council (NMRC) Centre Grant Programme (No. CG21APR1005).

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