Department of Chemistry, Korea University, Seoul 02841, Korea.
Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou 311200, China.
J Am Chem Soc. 2022 Jun 29;144(25):11326-11337. doi: 10.1021/jacs.2c03256. Epub 2022 Jun 16.
Pyroptosis, a newly characterized form of immunogenic cell death, is attracting increasing attention as a promising approach to cancer immunotherapy. However, biocompatible strategies to activate pyroptosis remain rare. Here, we show that a photocatalytic superoxide radical (O) generator, , triggers pyroptosis in cancer cells. was designed to take advantage of an intramolecular triplet-ground state splitting energy modulation approach. Detailed studies revealed that the pyroptosis triggered by under conditions of photoexcitation proceeds through a caspase-3/gasdermin E (GSDME) pathway rather than via canonical processes involving caspase-1/gasdermin-D (GSDMD). was found to function via a partial-O-recycling mode of action and to trigger cell pyroptosis and provide for effective cancer cell ablation even under conditions of hypoxia (≤2% O). In the case of T47D 3D multicellular spheroids, good antitumor efficiency and stemness inhibition are achieved. This work highlights how photocatalytic chemistry may be leveraged to develop effective pyroptosis-inducing agents.
细胞焦亡是一种新发现的免疫原性细胞死亡形式，作为癌症免疫治疗的一种很有前途的方法，正日益受到关注。然而，激活细胞焦亡的生物相容性策略仍然很少。在这里，我们展示了一种光催化超氧自由基 (O) 发生器 ， 可以在癌细胞中引发细胞焦亡。 是利用分子内三重态-基态分裂能量调节方法设计的。详细研究表明，在光激发条件下， 触发的细胞焦亡是通过半胱天冬酶-3/气鼓素 E (GSDME) 途径进行的，而不是通过涉及半胱天冬酶-1/气鼓素-D (GSDMD) 的经典途径。 被发现通过部分 O 循环作用模式发挥作用，并可引发细胞焦亡，并在缺氧 (≤2% O) 条件下有效地消融癌细胞。在 T47D 3D 多细胞球体的情况下，实现了良好的抗肿瘤效率和干性抑制。这项工作强调了光催化化学如何可以被利用来开发有效的诱导细胞焦亡的试剂。
