Multivalent supramolecular fluorescent probes for accurate disease imaging.

Optical imaging is a powerful tool for early disease detection and effective treatment planning, but its accuracy is often compromised by the uptake of imaging materials by the mononuclear phagocyte system (MPS). Herein, we leverage multivalent host-guest interactions between cyanine dyes and β-cyclodextrin polymers to develop supramolecular probes with enhanced stability, optical, and transport profiles for accurate in vivo imaging. These multivalent interactions not only ensure the stability of the probes but also enhance fluorescence efficiency by minimizing nonradiative decay. Our self-assembly approach effectively modulates probe size and surface properties, enabling evasion of MPS clearance and promoting prolonged bloodstream circulation, thereby improving the signal-to-background ratio for imaging. The effectiveness of our design is demonstrated by substantial advancements in the early diagnosis of acute kidney injury and by providing high-contrast imaging and precise surgical navigation across various tumor models. Our strategy not only advances optical imaging materials toward clinical translation but also establishes a versatile platform applicable to multiple imaging modalities.