A Supramolecularly Activatable Photosensitizer: Controllable Cyanine J-Aggregation for Efficient Photodynamic Therapy

An activatable photosensitizer that could induce phototoxicity only in target sites is highly demanded to overcome the potential off-target toxicity in photodynamic therapy. It is of great significance to design tailored photosensitizers with a new caging mechanism that can be activated by molecular signatures of pathogenic tissues. Herein, we report a novel supramolecularly activatable photosensitizer that employs cucurbit[7]uril (CB[7]) to regulate the J-aggregate and monomer state of a thio-pentamethine cyanine dye with alpha-naphthyl group on side arms (Naph-alpha-TCy5), switching its photosensitizing property between off-on states. The host-guest complex Naph-alpha-TCy5-CB[7] is a caged photosensitizer with a superior luminescence property in an aqueous solution. It could be effectively activated by polyamines in cancer cells through competitive host-guest complexation; then the restored J-aggregates of Naph-alpha-TCy5 could efficiently generate singlet oxygen. Eventually, the supramolecularly activatable Naph-alpha-TCy5-CB[7] demonstrated appreciable antitumor bioactivity in vivo with excellent biosafety. It is anticipated that this design strategy of supramolecularly activatable photosensitizers opens new horizons for efficient photodynamic therapy with specificity and safety.