  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.
