Biomimetic Organic Nanozyme as Tumor Vaccines for Targeted Suppression of Ammonia‐Induced T Lymphocyte Death to Augment Breast Cancer Immunotherapy
Meng Suo, Deyi Yang, Mingyue Yang, Jue Wang, Dingfeng Zhang, Daoming Zhu, Qingyong Xu, Yanni Song
Abstract
Abstract Ammonia‐induced T lymphocyte death (AITD) offers a new perspective on immune regulation after the activation of CD8 + T cells. However, the use of a single AITD inhibitor is constrained by multiple factors in the immunosuppressive tumor microenvironment and requires combination strategies to achieve breakthroughs. Herein, a rationally designed organic nanozyme (IR‐IHpd) is presented, integrating anthocyanin‐based near‐infrared photodynamic therapy (NIR‐PDT) and Hemin‐derived peroxidase (POD)‐like catalytic activity. Under 780 nm laser irradiation, it generates ROS through Type I/II photodynamic mechanisms while catalyzing H 2 O 2 into cytotoxic ·OH, establishing an uninterrupted ROS generation. Co‐encapsulated with CB‐839 in DSPE‐Hyd‐PEG and coated with dendritic cell (DC) membranes to form a biomimetic system (DMIC), this system targets both tumors and T cells. After intravenous administration, the DMIC nanozyme system efficiently accumulates in tumor tissues, tumor‐draining lymph nodes, and spleens, where NIR irradiation induces tumor immunogenic cell death while promoting DCs maturation and T cell activation. The DMIC also functions as a tumor vaccine, capable of directly activating T cells and preventing tumor occurrence. Furthermore, the released CB‐839 reduces intracellular ammonia levels in T cells, thereby enhancing anti‐tumor immunity. This pioneering work achieves targeted AITD inhibition for the first time, integrating NIR‐PDT, metabolic modulation, and immune activation to advance nanozyme‐based immunotherapy.