‍题目：The Tripartite Cascade Strategy Amplifies Cellular Oxidative Stress to Disrupt Oxidation–Reduction Homeostasis for Tumor Immunogenic Cell Death

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摘要：

Immunogenic cell death (ICD) induced by intracellular oxidation–reduction homeostasis imbalance is a classic mechanism in cancer immunotherapy. Herein, we propose a tripartite strategy to amplify cellular oxidative stress based on a combination of peptidic nanoparticles (TPFNO/CCA NPs) of host–guest drug-loading, fibrillar transformation, and NO generation. Cinnamaldehyde (CA) was released from TPFNO/CCA NPs due to Schiff base bond breakage within the lysosome, promoting excessive ROS generation. The residual TPFNO/C NPs bind the mitochondria, where excessive ROS induces the host–guest disintegration of ferrocene/β-cyclodextrin. The β-sheet TPFNO peptide could further transform into a fibrillar network on the mitochondria surface, leading to a further surge of ROS. Concurrently, the TPFNO peptide would locally release NO gas by consuming intracellular glutathione. NO further reacts with ROS and yields ONOO–, exacerbating mitochondrial dysfunction. Through a synergistic cascade of ROS generation and glutathione consumption, TPFNO/CCA NPs efficiently amplify oxidative stress, inducing potent immunogenic death in tumor cells.‍

全文链接：https://doi.org/10.1021/acsmaterialslett.4c02423