Universal NIR‐II‐Emitting Unimolecular Micelles with Tailorable Pharmacokinetic and Optical Properties for Adaptive Imaging

Abstract π‐Conjugated fluorophores show great potential for NIR‐II bio‐imaging owing to their superior brightness and photostability, yet their clinical translation has been hindered by suboptimal pharmacokinetics. To address this issue, a strategy is developed to tailor the in vivo behavior of π‐conjugate fluorophores by breaking π – π stacking in polymer brush‐engineered unimolecular micelles. This approach marks a significant shift from traditional methods of tuning micelles, which rely on varying the hydrophilic‐to‐hydrophobic ratios and are often ineffective for π‐conjugated systems due to the dominance of π – π interactions. By disrupting π – π interactions in the unimolecular micelles, pharmacokinetics and photophysical properties can be precisely controlled by systematically varying the molecular weight and composition of the polymer brushes. Accordingly, the blood circulation half‐life can be adjusted across a 60‐fold range, and fluorescence emissions are improved by 47‐fold, facilitating adaptive fluorophore applications from kidney dysfunction detection to tumor imaging. Additionally, the engineered unimolecular micelles exhibit reduced nonspecific uptake and improved tumor targeting efficiency, resulting in a 5‐fold higher tumor‐to‐liver ratio than conventional π – π stacked nano‐aggregates. These findings offer a solid solution to the pharmacokinetic optimization issues and provide a new design principle for π‐conjugated phototheranostic materials.