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

Abstract

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·4Cl and ExAnBox·4Cl, can effectively bind hypocrellin B (HB), a pharmaceutically active natural PS for PDT, with binding constants of the 10⁷ 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⊂AnBox⁴⁺ and HB⊂ExAnBox⁴⁺) 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⊂AnBox⁴⁺ and HB⊂ExAnBox⁴⁺ have different delivery effects at the cellular level.