Photoswitchable AIE photosensitizer for reversible control of singlet oxygen generation in specific bacterial discrimination and photocontrolled photodynamic killing of bacteria

• A novel DTE-based photoswitchable AIE photosensitizer has been developed. • It showed excellent AIE properties and photochromism in different solvents. • Excellent photoswitching behavior was observed in the water-soluble nanosystem. • Reversible control of 1 O 2 generation was achieved under 420 nm light irradiation. • It was successfully applied in imaging-guided photocontrolled antimicrobial PDT. The photosensitizer system that allows for reversible noninvasive control over singlet oxygen generation ( 1 O 2 ) is in great demand for precise photodynamic therapy (PDT) aimed at reducing non-specific damage to the normal cells or tissues. However, they often suffer from fluorescence quenching and insufficient 1 O 2 generation due to aggregation-caused quenching (ACQ) phenomenon in a hydrophilic and physiological environment, severely limiting their applications in both imaging and PDT therapy. Herein, a novel positively charged photoswitchable photosensitizer with aggregation-induced emission (AIE) has been rationally designed and successfully developed, in which pyridinium-tetraphenylethylene (Py-TPE) photosensitizing fragment and dithienylethene (DTE) switch unit were covalently linked through a flexible C4 chain enabling efficient intramolecular energy transfer between both functional entities, thus allowing for reversible control of 1 O 2 generation. Preliminary evaluation of the photophysical properties revealed excellent AIE properties and photoswitching behavior in various solvents. Furthermore, the nanoparticles (NPs) fabricated by the amphiphilic Pluronic F127 exhibited excellent photochromic performance in the aqueous medium. Significantly, 1 O 2 generation in the closed NPs was suppressed by the competitive energy transfer, while the generation of 1 O 2 in the open NPs was activated upon light irradiation, demonstrating its reversible control over 1 O 2 generation under irradiation with 420 nm light. As expected, it has been proved to perform well in specific bacterial discrimination and photocontrolled antimicrobial PDT against Staphylococcus aureus ( S. aureus) in vitro .