Recent advances in supramolecular chemistry research have led to the development of artificial chemical systems that can form self-assembled structures that imitate proteins involved in the regulation of cellular function. However, intracellular polymerization systems that operate inside living cells have been seldom reported. In this study, we developed an intramitochondrial polymerization-induced self-assembly system for regulating the cellular fate of cancer cells. It showed that polymeric disulfide formation inside cells occurred due to the high reactive oxygen species (ROS) concentration of cancer mitochondria. This polymerization barely occurs elsewhere in the cell owing to the reductive intracellular environment. The polymerization of the thiol-containing monomers further increases the ROS level inside the mitochondria, thereby autocatalyzing the polymerization process and creating fibrous polymeric structures. This process induces dysfunction of the mitochondria, which in turn activates cell necroptosis. Thus, this in situ polymerization system shows great potential for cancer treatment, including that of drug-resistant cancers.

中文翻译：

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线粒体内二硫化物聚合控制癌细胞命运

超分子化学研究的最新进展导致了人工化学系统的发展，这些系统可以形成自组装结构，模仿参与细胞功能调节的蛋白质。然而，鲜有报道在活细胞内运行的细胞内聚合系统。在这项研究中，我们开发了一种线粒体内聚合诱导的自组装系统，用于调节癌细胞的细胞命运。结果表明，由于癌症线粒体的高活性氧 (ROS) 浓度，在细胞内形成聚合二硫化物。由于还原性细胞内环境，这种聚合几乎不会发生在细胞的其他地方。含硫醇单体的聚合进一步增加了线粒体内的 ROS 水平，从而自动催化聚合过程并产生纤维状聚合物结构。这个过程会导致线粒体功能障碍，进而激活细胞坏死性凋亡。因此，这原位聚合系统在癌症治疗方面显示出巨大的潜力，包括耐药性癌症的治疗。