2. Academic Validation
  3. Lysosome Escape and Golgi Apparatus Accumulation Drive Robust Pyroptosis Based on Sulfhydryl-Inspired Aggregation-Induced Emission Photosensitizers

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

  • J Med Chem. 2025 Aug 14;68(15):16446-16458. doi: 10.1021/acs.jmedchem.5c01325.
Yucong Li 1,  Mengyan Tian 2,  Xinyue Zhao 1,  Yuming Chang 2,  Ruofei Wang 3,  Yaning Li 2,  Jun Guo 3,  Yi Liu 3 4,  Pai Liu 2
Affiliations

Affiliations

  • 1 State Key Laboratory of Advanced Separation Membrane Materials, School of Chemical Engineering and Technology, Tiangong University, Tianjin 300387, P. R. China.
  • 2 School of Materials Science and Engineering, Tiangong University, Tianjin 300387, P. R. China.
  • 3 School of Chemistry, Tiangong University, Tianjin 300387, P. R. China.
  • 4 Key Laboratory of Catalysis and Energy Materials Chemistry of Ministry of Education & Hubei Key Laboratory of Catalysis and Materials Science, School of Chemistry and Materials Science, South-Central Minzu University, Wuhan 430074, P. R. China.
PMID: 40673840 DOI: 10.1021/acs.jmedchem.5c01325
Abstract

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.

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