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

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.