Towards an Innate Cell-Environment Nanothermometer

Based on the PubMed database, there are around 260 manuscripts describing nanothermometers. These research articles detail the synthesis, performance, and application of intracellular nanothermometers. This intracellular prevalence is due to the significant importance, complexity, and utility of the intracellular compartments for understanding cell metabolism and disease treatment. However, in recent years, the extracellular environment of the cell has emerged as a crucial factor in medicine, particularly in hyperthermia and immunotherapy. Despite this, we have not seen evidence in the literature describing the utilization or performance of a nanothermometer designed for extracellular temperature measurements. This oversight not only neglects the potential for measuring extracellular temperature but also fails to address the extracellular environment of the cell. Here, we introduce a nanothermometer designed specifically for measuring extracellular temperature by directly converting serum proteins into nanothermometers (either unmodified or labeled with the clinically approved dye Fluorescein). Additionally, leveraging the extracellular localization of these nanothermometers, we demonstrate (1) the enhancement of their temperature sensitivity by combining them with gold nanorods, and (2) their capability to generate damage and disrupt the plasma membrane, thus opening the door to their use as photodynamic therapy agents. We firmly believe that these advancements represent not only a broadening of the applications of nanothermometry but also a pioneering step in showcasing the ability of nanothermometers to induce cell death.