Manganese-based nanoadjuvants for the synergistic enhancement of immune responses in breast cancer therapy via disulfidptosis-induced ICD and cGAS-STING activation

作者：Ke Zhang, Chengyao Huang, Yu Ren, Mingyue Zhang, Xiaotong Lu, Bangliu Yang, Peiran Chen, Shi‐Yao Guo, Xueqian Wang, Yuhong Zhuo, Chao Qi, Kaiyong Cai · 发表于：Biomaterials · 年份：2025 · DOI：10.1016/j.biomaterials.2025.123359 · 被引用次数：25 · 研究领域：Nanoplatforms for cancer theranostics、Advanced Nanomaterials in Catalysis、Extracellular vesicles in disease

Tumor immunotherapy represents one of the most promising strategies for combating tumors by activating the immune system , harnessing anti-tumor immune cells to eliminate tumor cells, and preventing tumor recurrence and metastasis. However, clinical data indicate that the anti-tumor immune response is often inadequate in many cancer patients, resulting in the failure of tumor immunotherapy . Herein, we report a manganese (Mn)-based nanoadjuvant (denoted as BMP-Au) aimed at synergistically enhancing anti-tumor immune responses in breast cancer therapy through disulfidptosis-induced immunogenic cell death and Mn-mediated cGAS-STING pathway activation. BMP-Au is synthesized using bovine serum albumin as a biotemplate for biomimetic mineralization of manganese phosphate nanosheets , followed by the deposition of gold nanoparticles (Au NPs) on their surface . By exploiting the glucose oxidase-like activity of Au NPs alongside the Fenton-like reaction facilitated by Mn 2+ , BMP-Au orchestrates a cascade catalytic reaction that generates reactive oxygen species from glucose. This process not only initiates disulfidptosis but also leads to DNA fragmentation crucial for activating the cGAS-STING pathway. These concurrent mechanisms compromise cancer cell viability while significantly enhancing tumor immunogenicity , positioning BMP-Au as an innovative nanoadjuvant for cancer treatment that leverages both cellular stress mechanisms and immune activation.