Supramolecular Assembly Based on Calix(4)arene and Aggregation‐Induced Emission Photosensitizer for Phototherapy of Drug‐Resistant Bacteria and Skin Flap Transplantation

Abstract Photodynamic therapy as a burgeoning and non‐invasive theranostic technique has drawn great attention in the field of antibacterial treatment but often encounters undesired phototoxicity of photosensitizers during systemic circulation. Herein, a supramolecular substitution strategy is proposed for phototherapy of drug‐resistant bacteria and skin flap repair by using macrocyclic p ‐sulfonatocalix(4)arene (SC4A) as a host, and two cationic aggregation‐induced emission luminogens (AIEgens), namely TPE‐QAS and TPE‐2QAS, bearing quaternary ammonium group(s) as guests. Through host–guest assembly, the obtained complex exhibits obvious blue fluorescence in the solution due to the restriction of free motion of AIEgens and drastically inhibits efficient type I ROS generation. Then, upon the addition of another guest 4,4′‐benzidine dihydrochloride, TPE‐QAS can be competitively replaced from the cavity of SC4A to restore its pristine ROS efficiency and photoactivity in aqueous solution. The dissociative TPE‐QAS shows a high bacterial binding ability with an efficient treatment for methicillin‐resistant Staphylococcus aureus ( MRSA ) in dark and light irradiation. Meanwhile, it also exhibits an improved survival rate for MRSA ‐infected skin flap transplantation and largely accelerates the healing process. Thus, such cascaded host–guest assembly is an ideal platform for phototheranostics research.