LAUSR

Artificial supramolecular systems capable of self‐assembly and that precisely function in biological media are in high demand. Herein, we demonstrate a highly specific host‐guest‐pair system that functions in living cells. A per‐O‐methyl‐β‐cyclodextrin derivative (R8‐B‐CDMe) bearing both an octaarginine peptide chain and a BODIPY dye was synthesized as a fluorescent intracellular delivery tool. R8‐B‐CDMe was efficiently taken up by HeLa cells through both endocytosis and direct transmembrane pathways. R8‐B‐CDMe formed a 2 : 1 inclusion complex with tetrakis(4‐sulfonatophenyl)porphyrin (TPPS) as a guest molecule in water, from which fluorescence resonance energy transfer (FRET) from R8‐B‐CDMe to TPPS was observed. The FRET phenomenon was clearly detected in living cells using confocal microscopy techniques, which revealed that the formed supramolecular R8‐B‐CDMe/TPPS complex was maintained within the cells. The R8‐B‐CDMe cytotoxicity assay revealed that the addition of TPPS counteracts the strong cytotoxicity (IC50=16 μM) of the CD cavity due to complexation within the cells. A series of experiments demonstrated the bio‐orthogonality of the supramolecular per‐O‐methyl‐β‐CD/tetraarylporphyrin host‐guest pair in living cells.