Bioorthogonal Disruption of Pyroptosis Checkpoint for High-Efficiency Pyroptosis Cancer Therapy

• DOI: 10.1021/jacs.3c04180
• Publication Date: 2023-07-24T13:17:40Z
• Authors: Wenting Zhang; Zhengwei Liu; Jiawei Zhu; Zhenqi Liu; Yu Zhang; Geng Qin; Jinsong Ren; Xiaogang Qu
• Keywords: Pyroptosis; Bioorthogonal Chemistry

Pyroptosis is an inflammatory form of programmed cell death that holds great promise in cancer therapy. However, autophagy as the crucial pyroptosis checkpoint and self-protective mechanism cells significantly weakens therapeutic efficiency. Here, a bioorthogonal nanoregulator constructed to induce disrupt checkpoint, enabling high-efficiency The allows situ synthesis accumulation photosensitizer PpIX mitochondria directly produce mitochondrial ROS, thus triggering pyroptosis. Meanwhile, generated inhibitor via palladium-catalyzed chemistry can boost efficacy. With biomimetic membrane coating, this platform for modulating presents specificity poses no harm normal tissue, resulting highly efficient safe antitumor treatment. To our knowledge, first report on disrupting intrinsic protective tumor This work highlights plays key regulative role therapy, which would motivate future design regimens.