Organic small-molecule NIR-II fluorophores for tumor phototheranostics

Cancer remains a major threat to human health. Phototheranostics, which integrates optical imaging with phototherapy, has emerged as a promising strategy. However, its clinical translation is hampered by intense light scattering and absorption in biological tissues, resulting in limited penetration depth. NIR-II fluorescence imaging provides significant advantages, such as reduced tissue scattering and autofluorescence, a higher signal-to-noise ratio, and greater tissue penetration. These advantages facilitate high-resolution imaging of deep-seated tumors. Among various NIR-II probes, organic small-molecule fluorophores are particularly attractive owing to their excellent biocompatibility, tunable photophysical properties, and high clinical translation potential. Nevertheless, clinically approved agents remain scarce and are largely confined to the NIR-I window. Therefore, developing bright and biocompatible organic small-molecule NIR-II fluorophores represents an urgent and critical goal in cancer phototheranostics.

In a new paper published in Light: Science & Applications, a team of scientists, led by Professor Quan Li from Institute of Advanced Materials, Southeast University, China, and Materials Science Graduate Program, Kent State University, USA, and co-workers have reviewed the recent advances in organic small-molecule NIR-II fluorophores for tumor phototheranostics. This work systematically summarizes molecular design strategies, methodologies for optimizing photophysical properties, and applications in tumor theranostics. The authors analyze representative fluorophore scaffolds, including cyanine, BODIPY, benzobisthiadiazole, xanthene, cyano-based derivatives, and small-molecule metal complexes. They highlight how rational molecular engineering can overcome long-standing challenges, such as low quantum yields, limited photostability, and aggregation-caused quenching. Furthermore, the review discusses recent progress in the application of NIR-II fluorophores for advanced bioimaging and phototherapy. These advances demonstrate that rational probe design facilitates precise tumor visualization, real-time image guidance, and efficient phototherapy. This work provides strategic guidance and inspiration for researchers designing next-generation, high-performance NIR-II organic small-molecule fluorophores to accelerate their clinical translation.