Tm³⁺-Based Downshifting Nanoprobes with Enhanced Luminescence at 1680 nm for In Vivo Vascular Growth Monitoring

Optical imaging in the 1500–1700 nm region, known as near-infrared IIb (NIR-IIb), shows potential for noninvasive in vivo detection owing to its ultrahigh tissue penetration depth and spatiotemporal resolution. Rare earth-doped nanoparticles have emerged as widely used NIR-IIb probes because of their excellent optical properties. However, their downshifting emissions rarely exhibit sufficient brightness beyond 1600 nm. This study presents tetragonal-phase thulium-doped nanoparticles (Tm 3+ -NPs) with core–shell–shell structures (CSS, LiYbF 4:3%Tm@LiYbF 4 @LiYF 4 ) that exhibit bright downshifting luminescence at 1680 nm. Enhanced luminescence is attributed to (1) the promoted nonradiative relaxation between the doping ions and (2) the maximized sensitization process. Additionally, this strategy was validated for NIR-IIb luminescence enhancement of erbium (Er 3+ )-doped NPs. After surface modification with PEGylated liposomes, tetragonal-phase Tm 3+ -NPs exhibited a prolonged blood cycle time, high colloidal stability, and good biocompatibility. Owing to the advantages of Tm 3+ -based probes in NIR-IIb imaging, in vivo thrombus detection and monitoring of angiogenesis and arteriogenesis were successfully performed in a mouse model of ischemic hind limbs.