Immunogenic cell death (ICD) is a rare immunostimulatory form of cell death that can improve the clinical outcomes of chemo‐immunotherapeutic combination regimens through the establishment of a long‐term cancer immunity. None of the clinically used DNA‐binding Pt^II complexes is considered a Type II ICD inducer. We generated a series of Pt^II‐carbene complexes by applying minor structural alterations to the scaffold of a Type II ICD inducer Pt‐NHC and compared their efficiency in triggering ICD‐related cellular responses and phagocytosis. We successfully identified PlatinER, a novel highly potent Pt^II candidate with superior ICD properties. Crucially, the magnitude of ICD‐associated phagocytosis induced upon exposure of cancer cells to Pt complexes was dependent on the levels of ER‐localized reactive oxygen species (ROS) generation, which underpins their mechanisms of action and provides a feasible approach for the design of more effective Type II ICD inducers.

中文翻译：

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PlatinER：一种高度有效的抗癌铂（II）复合物，可诱导内质网应激驱动的免疫原性细胞死亡。

免疫原性细胞死亡（ICD）是一种罕见的细胞死亡免疫刺激形式，可通过建立长期的癌症免疫力来改善化学免疫治疗组合方案的临床结果。临床上使用的任何DNA结合Pt ^II复合物均不被认为是II型ICD诱导剂。通过对^II型ICD诱导物Pt-NHC的支架进行微小的结构改变，我们生成了一系列Pt ^II-卡宾配合物，并比较了它们在触发ICD相关的细胞应答和吞噬作用方面的效率。我们成功鉴定出PlatinER，这是一种新型的高效Pt ^II具有ICD优异性能的候选人。至关重要的是，癌细胞暴露于Pt复合物后诱导的与ICD相关的吞噬作用的程度取决于ER定位的活性氧（ROS）生成的水平，这支持了其作用机理，为设计抗氧化剂提供了可行的方法。更有效的II型ICD诱导剂。