Abstract Near-infrared II (NIR-II) fluorophores possess transformative potential for biomedical applications, owing to their deep-tissue penetration, reduced tissue autofluorescence, and low phototoxicity. Recent breakthroughs in molecular engineering have accelerated the development of NIR-II organic small-molecule fluorophores based on versatile scaffolds, including cyanine, boron dipyrromethene, benzobisthiadiazole, xanthene, cyano-based derivatives, and small-molecule metal complexes. This review systematically summarizes the molecular engineering strategies, photophysical properties, and structure-function relationships of NIR-II fluorophores in the last five years. We highlight recent breakthroughs in their theranostic applications, including high-resolution deep-tissue imaging and efficient phototherapeutic modalities such as photodynamic and photothermal therapy. Finally, we present forward-looking perspectives on current challenges and emerging opportunities, aiming to provide insights for promoting continued innovation and clinical translation in this rapidly advancing field.
Xiang et al. (Mon,) studied this question.