Fluorogenic Squaraine Dendrimers for Background‐Free Imaging of Integrin Receptors in Cancer Cells

To overcome the limited brightness of existing fluorogenic molecular probes for biomolecular targets, we introduce a concept dendrimer probe, which undergoes polarity-dependent switching due to intramolecular aggregation-caused quenching its fluorophores. Based on rational design dendrimers with four and eight squaraine dyes, found that octamer bearing dyes through sufficiently long PEG(8) linker displays >400-fold fluorescence enhancement from water non-polar dioxane. High extinction coefficient (≈2,300,000 m−1 cm−1) resulted quantum yield (≈25 %) make this brightest environment-sensitive molecule reported date. Its conjugate cyclic RGD used at low concentration (3 nm) enables integrin-specific imaging cancer cells high signal-to-background ratio. The developed probe is “golden middle” between nanoparticles, combining small size, turn-on response brightness, important bioimaging.