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.
The development of technologies capable of early tumor detection is unquestionably demanded by physicians, as early diagnosis is key to achieve more efficient and less invasive treatments with improved outcomes. At the preclinical level, nanotechnology has already provided innovative solutions for tumor imaging and therapy, but it has failed to provide real early tumor diagnosis. In this work, an infrared nanothermometry-based approach toward early melanoma detection, based on the changes produced in the thermal relaxation dynamics of tissues as the tumor develops, is introduced. In vivo experiments demonstrate that detection of incipient tumors from their very onset is possible through monitoring changes in their thermal relaxation dynamics using Ag 2 S infrared luminescent nanothermometers. For a total tumor development time of 14 days, luminescence nanothermometry allows tumor detection 6 days before its presence is evident by visual inspection. Simultaneous study of the tumoral vasculature reveals that the premature variation in the thermal relaxation dynamics is a consequence of the interplay between tumor angiogenesis and necrosis during the different tumor development stages.
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