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

Adv Healthc Mater. 2024 Apr;13(9):e2303336. doi: 10.1002/adhm.202303336. Epub 2024 Jan 16.

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.

Keywords: aggregation‐induced emission; calixarene; multidrug‐resistant bacteria; skin flaps; supramolecular assemblies.

MeSH terms

  • Calixarenes*
  • Methicillin-Resistant Staphylococcus aureus*
  • Phenols*
  • Photochemotherapy* / methods
  • Photosensitizing Agents / chemistry
  • Phototherapy
  • Reactive Oxygen Species

Substances

  • Photosensitizing Agents
  • calix(4)arene
  • Reactive Oxygen Species
  • Phenols
  • Calixarenes