Intermediate Layer‐Engineered Lanthanide Nanoparticles Enable Deep Bioorthogonal Liver Tumor and Vascular Imaging via Switchable NIR‐II Emissions

Abstract The second near‐infrared window (NIR‐II) has become an attractive optical region for fluorescence imaging. However, due to the complexity in vivo, NIR‐II light with various wavelengths for different imaging scenes has not been investigated. Here, we found that 1525 nm light is suitable for high‐resolution fluorescence imaging due to low background interference, while its attenuation in vivo makes it unsuitable for deep imaging. The 1064 nm light is suitable for deep imaging. The impact of Yb 3+ ions and the proportion of the intermediate layer in lanthanide nanoparticles on the modulation of emissions were investigated. The intense 1064 nm emission is achievable when the Yb 3+ content is 80% and the intermediate layer proportion is 0.1. The bioorthogonal orthotopic liver tumor imaging could be achieved by modifying the lanthanide nanoparticles with DBCO‐PEG 2000 ‐DSPE and establishing artificial receptors by N‐azidoacetylmannosamine‐tetraacylated (Ac 4 ManNAz). Lanthanide nanoparticles with the intermediate layer proportion of 0.66 and 80% Yb 3+ facilitate intense 1525 nm emission, enabling the vascular imaging. Based on the imaging characteristics of NIR‐II emissions with different wavelengths in vivo, this work achieves high‐resolution imaging and deep imaging through intermediate layer regulation of lanthanide nanoparticles, providing an opportunity to explore a new generation of high‐performance fluorescent probes.