Supramolecular photosensitizers using extended macrocyclic hosts for photodynamic therapy with distinct cellular delivery

The photosensitizers (PSs) for photodynamic therapy (PDT) mostly possess conjugated skeletons that are over-sized and poorly water-soluble to be encapsulated by conventional macrocyclic receptors. Herein, we report that two fluorescent hydrophilic cyclophanes, AnBox center dot 4Cl and ExAnBox center dot 4Cl, can effectively bind hypocrellin B (HB), a pharmaceutically active natural PS for PDT, with binding constants of the 10(7) level in aqueous solutions. The two macrocycles feature extended electron-deficient cavities and can be facilely synthesized through photo-induced ring expansions. The corresponding supramolecular PSs (HB subset of AnBox(4+) and HB subset of ExAnBox(4+)) exhibit desirable stability, biocompatibility, and cellular delivery, as well as excellent PDT efficiency against cancer cells. In addition, living cell imaging results indicate that HB subset of ExAnBox(4+) and HB subset of ExAnBox(4+) have different delivery effects at the cellular level.

Automated summary

Researchers report two fluorescent hydrophilic cyclophanes that can effectively bind hypocrellin B (HB), a commonly used photosensitizer for photodynamic therapy (PDT), with high binding constants in aqueous solutions. The macrocycles have extended electron-deficient cavities and can be easily synthesized through photo-induced ring expansions. The resulting supramolecular PSs show desirable stability, biocompatibility, and cellular delivery, as well as excellent PDT efficiency against cancer cells. Moreover, cell imaging results indicate different delivery effects at the cellular level for the two supramolecular PSs.