Spiky metal-organic framework nanosystem for enhanced cuproptosis-mediated cancer immunotherapy

作者：Manman Xu, Hengwen Chen, Guanghui Zhu, Xiaoyu Zhu, Ruike Gao, Bowen Xu, Xiaotong Song, Xinpu Han, Tianyu Shao, Qianhui Sun, Zhigang Xiao, Heping Wang, Ying Zhang, Yang Ge, Jie Li · 发表于：Nano Today · 年份：2024 · DOI：10.1016/j.nantod.2024.102231 · 被引用次数：30 · 研究领域：Metal-Organic Frameworks: Synthesis and Applications、Nanoplatforms for cancer theranostics、Advanced Nanomaterials in Catalysis

Immunotherapy, particularly αPD-1 therapy, has been hailed as a significant breakthrough in cancer treatment. However, the limited response rates and unknown mechanisms hinder the clinical application of αPD-1 blockade boosting with hybrid nanoparticles. Herein, we introduce a strategy to enhance cancer immunotherapy by leveraging cuproptosis, initiated by the spiky copper-based metal-organic framework (S@Cu-MOF) loaded with polyphyllin I (PPI) and synergized with αPD-1 therapy. Interestingly, the unique spiky structure of S@Cu-MOF not only significantly enhances tumor cell uptake but also leads to pronounced DNA damage. The application of S@Cu-MOF/PPI with αPD-1 therapy led to obvious tumor regression and prolonged survival due to cuproptosis, which involved substantial mitochondrial damage. This process amplifies the cGAS/STING immune pathway, enhancing the immune response against cancer. Additionally, this strategy promoted immunogenic cell death (ICD), recruitment of mature dendritic cells (DCs), T cell-mediated immunity, and effective memory CD8+ T cells, resulting in significant abscopal tumor suppression and lung metastasis reduction. Our study highlights the potential of S@Cu-MOF/PPI as a sensitizer for αPD-1 with the mechanism of cuproptosis and the cGAS/STING pathway, offering a promising strategy for the next generation of immunotherapy.