Orchestrated Strategies for Developing Fluorophores for NIR‐II Imaging

Abstract Fluorescence imaging (FLI), a non‐invasive, real‐time, and highly sensitive imaging modality, allows for investigating the molecular/cellular level activities to understand physiological functions and diseases. The emergence of the second near‐infrared window (NIR‐II, 1000–1700 nm) has endowed fluorescence imaging with deeper tissue penetration and unprecedented clarity. Among the various NIR‐II imaging fluorophores, the organic fluorescent probes have occupied a pivotal position in bioimaging due to their higher biocompatibility, safety, and potential for clinical applications compared with those of the inorganic probes. To obtain high‐quality organic dyes, diverse strategies have been taken. In this review, different strategies for optimizing NIR‐II organic fluorophores are summarized, including traditional chemical modifications, and emerging bioengineering operations, which have not previously been elaborated on and summarized. Moreover, the bioengineering strategies are highlighted using endogenous serum proteins and even exogenous gene‐editing proteins, which would provide fresh insights to design good‐performance dyes and help develop NIR‐II probes with clinical translation potential in the future. A critical perspective on the direction of the design strategies of NIR‐II dyes for disease imaging is also proposed.