Ce 3+ ‐Mediated Self‐Calibrating NIR‐II Nanothermometer Enables Reliable Real‐Time In Vivo Temperature Monitoring

ABSTRACT Precise temperature monitoring in living systems provides valuable insights into physiological processes, thereby motivating the development of luminescent nanothermometers for noninvasive thermometry. However, wavelength‐dependent tissue absorption and scattering inevitably distort luminescence signals, resulting in inaccurate temperature measurements. Here, we report a self‐calibrating luminescent nanothermometer (NaYF 4 : Tm@NaYF 4 : Er@NaYF 4 @NaYbF 4 : Er/Tm/Ce@NaYF 4 ) that utilizes the Er 3+ and Tm 3+ emissions at 1532 and 1626 nm in the low‐scattering long‐wavelength near‐infrared region (NIR‐II‐L, 1500–1900 nm) to achieve reliable in vivo thermometry. By identifying Ce 3+ as a critical mediator that suppresses temperature‐sensitive phonon‐assisted energy transfer (PAT) between Tm 3+ and Er 3+ , we inversely engineered the Ce 3+ ‐doped Tm 3+ /Er 3+ outer module to generate a thermally inert reference ratio for calibrating the PAT‐enhanced thermometric ratio of the inner Tm 3+ /Er 3+ module. The resulting self‐calibrating signal minimized depth‐induced distortion with only 2.9% fluctuation through 10 mm of tissue, enabling reliable dynamic thermometry at a high temporal resolution of 20 fps. In vivo studies further demonstrated that the nanothermometer enabled accurate intestinal thermometry and intratumoral temperature monitoring during photothermal therapy. This work provides new insights into self‐calibrating luminescent nanoprobes for accurate real‐time sensing in living systems.