Unimolecular Micellization Strategy for Achieving NIR‐II Excited Fluorophores with Enhanced Brightness in Aqueous Media

Abstract Fluorescence imaging in the second near‐infrared window (NIR‐II) enables deep‐tissue visualization with high spatial–temporal resolution. Developing molecular fluorophores with high brightness and stability in aqueous media is therefore critical. However, most NIR‐II excited fluorophores suffer from pronounced nonradiative decay and fluorescence quenching in water. Here, we propose a unimolecular micellization strategy to construct high‐brightness NIR‐II fluorophores that self‐assemble into stable unimolecular micelles (UIMs) in aqueous solution. The designed star‐shaped amphiphilic molecule IR‐FCT8CP carries long alkyl chains that collapse into a compact hydrophobic core upon micellization, effectively shielding the fluorophore from water‐induced quenching and restricting intermolecular interactions. The resulting IR‐FCT8CP UIMs exhibit absorption and emission maxima at 979 and 1181 nm, respectively, with a quantum yield of 0.05% and a molar absorption coefficient of 1.67 × 10 4 M −1 ·cm −1 in aqueous solution, yielding higher brightness than IR‐FCDP and IR‐FCTP UIMs. The IR‐FCT8CP UIMs enable dynamic in vivo vascular imaging under 1064 nm excitation using a 1500 nm long‐pass filter, clearly resolving vascular networks with a high signal‐to‐background ratio. This unimolecular micellization strategy offers a general design concept for developing stable, high‐brightness NIR‐II molecular fluorophores for efficient bioimaging in physiological environments.