Tunable and Enhanced NIR-II Luminescence from Heavily Doped Rare-Earth Nanoparticles for In Vivo Bioimaging

The last decade has witnessed the booming development of optical imaging in the second near-infrared (NIR-II, 1000-1700 nm) window for disease screening and image-guided surgical interventions, due to the merits of multi-color observations and high spatio-temporal resolution in deep tissue. Therefore, bright and multispectral NIR-II probes are required and play a key role. Here, we report the synthesis of a set of bright rare-earth based NIR-II downshifting nanoparticles (DSNPs) with hexagonal phase (β phase). As compared with the widely reported DSNPs (β-NaYF4@NaYF₄:20Yb/(0.5-2)A@NaYF₄; A = Ho, Pr, Tm or Er) previously, we reveal that the concentrations of both sensitizers and activators can be further highly doped, not limited by the concentration quenching effect. Our results demonstrate that the optimized formula in the heavily doped DSNPs (β-NaYF₄@NaYbF₄:A@NaYF₄, A = 20Ho, 3Pr, 4Tm or 10Er) leads to 1.2- to 4.2-folds NIR-II luminescence enhancement. Especially for the heavily Er-doped DSNPs with long-wavelength photons extending to the NIR-IIb window (1500-1700 nm), we can further boost their luminescence through introducing a beneficial cross-relaxation and host matrix with higher phonon energy (cubic phase NaYF₄@NaYbF₄:10Er/5Ce@NaYF₄), leading to a total of ∼11.4-fold enhancement. The resulting biocompatible, bright NIR-II emitting DSNPs enable us to in vivo monitor the cerebral vessels through the intact scalp and skull, as well as two-color dynamic tumor imaging with high spatial resolution. This work suggests the potential of the heavily doped DSNPs for multiplexed imaging in cerebrovascular abnormalities toward the diagnosis and therapy of the cerebral diseases.