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.