A Chromatic Nanoswitcher for Thermal Monitoring of Cell Metabolism

Abstract Accurate sensing of intracellular temperature is crucial for understanding and monitoring cell metabolism, serving as an initial step toward diagnosing conditions such as mitochondria‐related diseases. However, thermal monitoring of cell metabolism is challenging due to the minimal temperature variations caused by intracellular metabolic activity (typically ≈1 °C) and by the risk of crosstalk in intracellular sensors. A novel type of intracellular thermal sensor is presented, based on silica nanocapsules filled with a thermo‐responsive fluorescent medium. This medium undergoes a reversible phase transition from solid to liquid at temperatures ≈37 °C, inducing a chromatic switch that facilitates remote thermal sensing. The chromatic switchers exhibit a thermal sensitivity of ≈13% °C⁻¹ at 37 °C, one of the highest reported for intracellular thermal sensing. Notably, the thermal response is unaffected by external factors such as pH, ionic strength, and viscosity. Moreover, it is confirmed that the response of the sensors is not affected by the cellular activity, underscoring their reliability for cytoplasmic temperature measurements. The potential of these sensors is demonstrated by measuring intracellular heating during the metabolic switch from mitochondrial to glycolytic activity, showcasing their potential for real‐time, precise thermal monitoring (<1 °C) of cell metabolism.