Supramolecular caging for cytosolic delivery of anionic probes

The cytosolic delivery of hydrophilic, anionic molecular probes and therapeutics is a major challenge in chemical biology and medicine. Herein, we describe the design and synthesis of peptide–cage hybrids that allow an efficient supramolecular binding, cell membrane translocation and cytosolic delivery of a number of anionic dyes, including pyranine, carboxyfluorescein and several sulfonate-containing Alexa dyes. This supramolecular caging strategy is successful in different cell lines, and the dynamic carrier mechanism has been validated by U-tube experiments. The high efficiency of the reported approach allowed intracellular pH tracking by exploiting the ratiometric excitation of the pyranine fluorescent probe.