Neodymium‐Doped Nanocrystals for Sensing Cellular Temperature at the Nanoscale

ABSTRACT Precise temperature monitoring in living cells is crucial for localized hyperthermia in cancer treatment, as heterogeneous heating can limit both efficacy and safety. Sub‐micron thermal measurements are therefore essential for effective therapy, but highly challenging. To address this, luminescent nanothermometers such as lanthanide‐doped nanocrystals have been investigated for accurate spatiotemporal thermal monitoring in cells. In this study, highly luminescent neodymium‐doped sodium yttrium fluoride nanocrystals (Nd‐NCs) were synthesized by adjusting dopant concentration and inert shelling to optimize near‐infrared photoluminescence (PL). Standard curves for temperature readout were developed using ratiometric analysis of temperature‐dependent PL spectra, showing excellent linearity and high thermal sensitivity. To improve aqueous stability and biocompatibility, a silica shell was added. Following incubation in A549 cells, imaging of nanoscale Nd‐NC luminescence spots enabled localized intracellular thermal readouts. Co‐incubation with silica‐coated gold nanostars (AuNS) allowed real‐time temperature measurements during photothermal therapy (PTT). Our results revealed a highly heterogeneous distribution of plasmon‐induced heating within the intracellular environment, with nanoscale hotspots and significant thermal gradients during PTT. To our knowledge, this is the first report of nanoscale luminescent nanothermometry performed during cellular hyperthermia, providing sub‐cellular insight into heat distribution and positioning Nd‐NC nanothermometers as powerful preclinical tools for guiding the design and improvement of nanoparticle‐mediated hyperthermia.