Molecular Engineering Boosts Photon-Activated Immunotherapy for Prostate Cancer Through Concurrent Pyroptosis and
Cheng Zhang1, Xiaolan Yin1, Jeongyeon Hong2,3
1Cancer Hospital of Dalian University of Technology, State Key Laboratory of Fine Chemicals, MOE Key Laboratory of Bio-Intelligent Manufacturing, School of Bioengineering, Dalian University of Technology, Dalian, China.
Angewandte Chemie (International Ed. in English)
|July 23, 2026
Summary
New photosensitizers enhance photodynamic immunotherapy for prostate cancer by generating reactive oxygen species (ROS) and activating anti-tumor immunity, leading to tumor eradication and suppression of metastasis.
Area of Science:
- Biomedical Engineering
- Cancer Research
- Photochemistry
Background:
- Prostate cancer treatment faces challenges including metastasis, drug resistance, and toxicity.
- Photodynamic immunotherapy (PDIT) shows promise but requires effective photosensitizers.
- Current photosensitizers need to generate reactive oxygen species (ROS) and activate antitumor immunity.
Purpose of the Study:
- To develop novel photosensitizers for enhanced photodynamic immunotherapy (PDIT).
- To engineer thiophene-based dyes for improved ROS generation and immune activation.
- To investigate the mechanism of action for multi-organelle localized photosensitizers.
Main Methods:
- Molecular engineering of triphenylamine (D) and N-ethyl-benzoselenazolium iodide (Se) (DTSe)-based photosensitizers.
- Modulation of π-conjugated structures, including carbazole unit incorporation.
- Assessment of photophysical properties (fluorescence, Huang-Rhys factor, energy gap, triplet lifetime).
- In vivo evaluation of tumor eradication and metastasis suppression.
Main Results:
- Carbazole incorporation in DZTSe suppressed fluorescence and enhanced ROS generation.
- DZTSe demonstrated multi-organelle localization in endoplasmic reticulum and mitochondria.
- DZTSe induced pyroptosis and activated the cGAS-STING pathway, reprogramming the tumor microenvironment.
- Effective eradication of primary tumors and suppression of distant lesions in vivo.
Conclusions:
- Engineered DZTSe photosensitizers offer a dual stress-immune activation strategy.
- This approach overcomes limitations of current prostate cancer therapies.
- DZTSe provides a molecular blueprint for developing advanced immune-activating photosensitizers.
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