An Emerging Toolkit of Ho3+ Sensitized Lanthanide Nanocrystals with NIR-II Excitation and Emission for in Vivo Bioimaging.

Optical imaging in the second near-infrared window (NIR-II, 1000-1700 nm) holds great promise for biomedical detection due to reduced tissue scattering and autofluorescence. However, the rational design of NIR-II probes with superior excitation wavelengths to balance the effects of tissue scattering and water absorption remains a great challenge. To address this issue, here we developed a series of Ho3+-sensitized lanthanide (Ln) nanocrystals (NaYF4: Ho, Ln@NaYF4) excited at 1143 nm, featuring tunable emissions ranging from 1000 to 2200 nm for in vivo bioimaging. Precise core-shell engineering (β-NaYF4: Ho@NaYF4: Ln@NaYF4 and β-NaYF4: Ho/Yb@NaYbF4@NaYbF4: Ln@NaYF4) further endows the Ho3+-sensitized system with the capability of energy migration within interfaces, enabling more abundant visible and NIR-II emissions that are unattainable in co-doped structures due to detrimental cross relaxation. Tissue phantom studies demonstrated the superior tissue penetration ability of 1143 photons, especially in imaging experiments through the highly photon-scattering skull, where the fluorescence transmittance of 1143 nm excited nanocrystals was 15% and 10% higher than that of the conventional 808 and 980 excitation, respectively. By leveraging these Ho3+-sensitized nanomaterials with multiemission characteristics and well-selected lanthanide nanomaterials with crosstalk-free excitation, we achieved six-channel NIR-II in vivo imaging, enabling the simultaneous visualization of blood vessels, liver, spleen, stomach, intestine, subcutaneous tumors, and lymph nodes in mice. Our research provides new insights into the design of lanthanide nanocrystals with NIR-II excitation and emission and highlights the potential of these materials in in vivo multichannel detection.