Lysosome Escape and Golgi Apparatus Accumulation Drive Robust Pyroptosis Based on Sulfhydryl-Inspired Aggregation-Induced Emission Photosensitizers

The prolonged residence time of photosensitizers (PSs) at the subcellular compartment was proposed as a smart approach to enhance the efficiency of oxidative damage in photodynamic therapy. However, before reaching an interested organelle, small molecules during the internalization process suffered acidic conditions and hydrolases in lysosomes, which finally hindered more than 90% when arriving into targets. Herein, we synthesized a small-molecule PS (BTF-DNBS) with GSH-activatable tumoral identification, lysosome-escape, and Golgi apparatus-triggered pyroptosis. Capitalizing on the distinct intracellular glutathione concentration gradient between normal and malignant cells, BTF-DNBS achieved selective cancer cell recognition through photoinduced electron transfer mechanism disruption. Interestingly, activated BTF-DNBS accumulated from lysosomes to the Golgi apparatus through the formation of rod-like stacking and triggered a Golgi apparatus-mediated pyroptosis. The antimetastatic immune response was provoked and successfully inhibited the growth of recrudescent tumor.