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

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 × 10⁴ 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.