2026-06-15
Recently, Zhang Dongsheng, a young faculty member at the School of Chemistry and Chemical Engineering, Henan Normal University, have published a research paper entitled “Mitochondria-Targeted Photodynamic Agents Drive Robust Pyroptosis by Caspase-3/GSDME Activation and Cardiolipin Externalization in Angewandte Chemie International Edition. Zhang Dongsheng is the first author; Dr. Teng Kunxu and Professor Yang Qingzheng of Beijing Normal University serve as co-corresponding authors. Henan Normal University is the first author’s affiliation.
This study proposes a novel strategy for efficiently inducing cellular pyroptosis via mitochondria-targeted photosensitizers. Pyroptosis is a highly immunogenic form of programmed cell death that activates antitumor immune responses through the release of inflammatory mediators and damage-associated molecular signals. In recent years, the use of photodynamic therapy to induce pyroptosis in tumor cells has attracted wide attention; however, achieving efficient induction of pyroptosis remains an important challenge in this field. To address this challenge, the research team proposed a synergistic activation design strategy and constructed a series of mitochondria-targeted supramolecular photosensitizers. These photosensitizers can specifically accumulate in mitochondria and efficiently generate reactive oxygen species upon light irradiation, simultaneously activating the Caspase-3/GSDME pathway and promoting cardiolipin externalization, thereby inducing mitochondrial membrane pore formation, accelerating the release of mitochondrial contents, establishing a continuously amplifying positive-feedback pyroptotic cascade, and ultimately driving cellular pyroptosis.
This study is the first to achieve efficient induction of cellular pyroptosis through mitochondria-targeted photodynamic therapy via the synergistic activation of the Caspase-3/GSDME pathway and cardiolipin externalization, providing new insights for the development of pyroptosis-targeted photosensitizers and advancing photodynamic therapy research. The research was supported by the National Natural Science Foundation of China, the China Postdoctoral Science Foundation, and other funding programs.
Paper link: https://onlinelibrary.wiley.com/doi/10.1002/anie.7359094
(Li Bin, Wang Manman, School of Chemistry and Chemical Engineering: )
