@article{Zhou2022, 
author = {Junjie Zhou and Xianbin Ma and Hao Li and Derun Chen and Liang Mao and Leilei Yang and Tian Zhang and Wei Qiu and Zhigang Xu and Zhi-Jun Sun},
title = {Inspired heat shock protein alleviating prodrug enforces immunogenic photodynamic therapy by eliciting pyroptosis},
year = {2022},
journal = {Nano Research},
volume = {15},
number = {4},
pages = {3398-3408},
keywords = {immunotherapy, photodynamic therapy, tumor microenvironment, heat shock proteins, pyroptosis},
url = {https://www.sciopen.com/article/10.1007/s12274-021-3946-2},
doi = {10.1007/s12274-021-3946-2},
abstract = {Despite immunotherapy involving immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, the clinical efficacy is limited due to ICI resistance. Pyroptosis is a gasdermin-mediated programmed cell death that enhances responses to ICIs. However, nontargeted elicitation of pyroptosis may induce systemic side effects and toxicity. Therefore, we reasonably design and construct a tumor-specific prodrug that combines the heat shock protein 90 inhibitor tanespimycin (17-AAG) with the photosensitizer chlorin e6 (Ce6) to induce pyroptosis, by utilizing the high glutathione level in the tumor microenvironment. The released Ce6 and 17-AAG produce reactive oxygen species by laser triggering, which induces gasdermin E-mediated pyroptosis. Furthermore, 17-AAG reduces myeloid-derived suppressor cells and sensitizes tumors to anti-programmed death-1 (PD-1) therapy. Thus, our prodrug strategy achieves tumor-targeted pyroptosis to suppress tumor growth, thereby improving the response to anti-PD-1 therapy and extending the survival of 4T1 breast tumor-bearing mice. Consequently, this pyroptosis-based prodrug represents a novel strategy for enforcing immunogenic photodynamic therapy.}
}