Boosted Energy Migration System in NIR‐IIc Rare‐Earth Nanoprobe for Deep‐Tissue Multiplexed Bioimaging

ABSTRACT Rare‐earth nanoparticles represent a promising class of NIR‐IIc emitters for deep‐tissue bioimaging beyond 1700 nm; however, the practical application remains limited by their suboptimal luminescence brightness and the low quantum efficiency (QE) of current detectors. Here we report a dual‐sensitizer rare‐earth nanoprobe (YbEr:Tm) that strategically steers Er‐Er energy migration into the favorable 4 I 13/2 → 4 I 13/2 channel, yielding a 43.5‐fold enhancement of Tm 3+ emission in the NIR‐IIc window. The resulting YbEr:Tm nanoprobes afford 180 µm spatial resolution through 1.5 cm of thoracic muscle, even under the constraints of a low‐QE extended‐range InGaAs detector. Building on this brightness, we achieve the first dynamic multiplexed NIR‐IIc in vivo bioimaging by exploiting the lifetime disparity between rare‐earth nanoprobes and PbS quantum dots. Furthermore, an implantable three‐plex NIR‐IIc optical cipher is devised, in which distinct nanoprobes with orthogonal lifetimes and spectral profiles enable information encryption within subcutaneous tissue and real‐time, noninvasive retrieval.