Oxidative Stress Amplifiers as Immunogenic Cell Death Nano-inducers Disrupting Mitochondrial Redox Homeostasis for Cancer Immunotherapy.

Reactive oxygen species (ROS)-induced oxidative stress in the endoplasmic reticulum (ER) is generally believed to be an important prerequisite for immunogenic cell death (ICD) which can trigger antitumor immune responses for cancer immunotherapy. However, little is known between the oxidative stress in a certain organelle other than ER and ICD till far. Herein, we designed polymers for preparing ROS-responsive nanoparticles (NP-I-CA-TPP) with mitochondrial targeting performance as ICD nano-inducers. We believe that NP-I-CA-TPP can target mitochondria which are extremely important organelles intimately involved in cellular stress signaling to play an important role in the induction of ICD. NP-I-CA-TPP could amplify cinnamaldehyde (CA)-induced ROS damage by iodo-thiol click chemistry-mediated glutathione (GSH) depletion in cancer cells. Finally, NP-I-CA-TPP was shown to disrupt mitochondrial redox homeostasis, amplify mitochondrial oxidative stress, promote cancer cell apoptosis via inducing ICD and triggering the body's anti-tumor immune response for cancer immunotherapy. This article is protected by copyright. All rights reserved.