Despite attracting increased attention from clinicians, brain temperature distribution, fluctuations and changes in response to external stimuli are still largely unknown and refractory to conventional temperature-probing approaches. Fluorescence nanothermometry in the second near-infrared window (NIR-II window, 1,000-1,700 nm), as shown here, can provide contactless brain thermal sensing through the scalp and skull in real time with a subdegree resolution. As a proof of concept, Ag 2 S nanothermometers have been used to monitor brain thermoregulation in a cooling/heating process and temperature changes associated to a barbiturate coma. 3 1. Introduction.

nanoheaters with multiparameter sensing for reliable thermal feedback during in vivo tumor therapy.

Optical probes operating in the second near-infrared window (NIR-II, 1,000-1,700 nm), where tissues are highly transparent, have expanded the applicability of fluorescence in the biomedical field. NIR-II fluorescence enables deep-tissue imaging with micrometric resolution in animal models, but is limited by the low brightness of NIR-II probes, which prevents imaging at low excitation intensities and fluorophore concentrations. Here, we present a new generation of probes (Ag 2 S superdots) derived from chemically synthesized Ag 2 S dots, on which a protective shell is grown by femtosecond laser irradiation. This shell reduces the structural defects, causing an 80-fold enhancement of the quantum yield. PEGylated Ag 2 S superdots enable deep-tissue in vivo imaging at low excitation intensities (<10 mW cm −2) and doses (<0.5 mg kg −1), emerging as unrivaled contrast agents for NIR-II preclinical bioimaging. These results establish an approach for developing superbright NIR-II contrast agents based on the synergy between chemical synthesis and ultrafast laser processing.