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

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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.

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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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Correspondence to Zhendong Yu, Jing Mu or Xiaoyuan Chen.

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

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Li, H., Zhong, Y., Wang, S. et al. In vivo bioorthogonal labeling of rare-earth doped nanoparticles for improved NIR-II tumor imaging by extracellular vesicle-mediated targeting. Nano Res. 16, 2895–2904 (2023). https://doi.org/10.1007/s12274-022-5033-8

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