Herein, a set of optogenetic tools (designated LiPOP) that enable photoswitchable necroptosis and pyroptosis in live cells with varying kinetics, is introduced. The LiPOP tools allow reconstruction of the key molecular steps involved in these two non-apoptotic cell death pathways by harnessing the power of light. Further, the use of LiPOPs coupled with upconversion nanoparticles or bioluminescence is demonstrated to achieve wireless optogenetic or chemo-optogenetic killing of cancer cells in multiple mouse tumor models. LiPOPs can trigger necroptotic and pyroptotic cell death in cultured prokaryotic or eukaryotic cells and in living animals, and set the stage for studying the role of non-apoptotic cell death pathways during microbial infection and anti-tumor immunity.

中文翻译：

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非凋亡细胞死亡的光遗传学控制

在此，介绍了一组光遗传学工具（指定为 LiPOP），可在具有不同动力学的活细胞中实现光开关坏死和细胞焦亡。LiPOP 工具允许通过利用光的力量重建这两种非凋亡细胞死亡途径中涉及的关键分子步骤。此外，LiPOPs 与上转换纳米粒子或生物发光的结合被证明可以在多个小鼠肿瘤模型中实现对癌细胞的无线光遗传学或化学光遗传学杀伤。LiPOPs 可以在培养的原核或真核细胞以及活体动物中引发坏死性和焦亡性细胞死亡，并为研究非凋亡细胞死亡途径在微生物感染和抗肿瘤免疫过程中的作用奠定基础。