Rational Design of High-Performance Hemithioindigo-Based Photoswitchable AIE Photosensitizer and Enabling Reversible Control Singlet Oxygen Generation

A photosensitizer furnishing with reversible control singlet oxygen generation (O-1(2)) is highly desirable for precise photodynamic therapy (PDT), lessening non-specific harm to healthy tissues. Here, a novel photoswitchable aggregation-induced emission (AIE) photosensitizer based on a triarylamine (TPA)-modified hemithioindigo (HTI), 6Br-HTI-TPA-OMe, was rationally designed. The triarylamine AIE photosensitizing moiety and HTI switch unit were covalently linked in one molecule, permitting reversible regulation of O-1(2) production. The photophysical evaluations revealed that 6Br-HTI-TPA-OMe possessed excellent AIE properties and Z/E photoswitch performance in different solvents. Additionally, the amphiphilic phospholipid-fabricated nanoparticles (NPs) also exhibited photochromic behavior in water. The Z-NPs initiated the generation of O-1(2) upon 520 nm light-emitting diode (LED) irradiation, but after switching to E-NPs, the generation of O-1(2) was inhibited by the competitive energy transfer, suggesting that reversible Z/E isomerization could photocontrol O-1(2) generation. The in vitro anti-tumor experiment verified that the 6Br-HTI-TPA-OMe can act as a photoswitchable AIE photosensitizer. This is the first report on the photoswitchable AIE photosensitizer of HTI-based molecules, to the best of our knowledge.