Organic small-molecule NIR-II fluorophores for tumor phototheranostics

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.