期刊
THERANOSTICS
卷 12, 期 14, 页码 6207-6222出版社
IVYSPRING INT PUBL
DOI: 10.7150/thno.75323
关键词
Immunotherapy; ferroptosis; fluorouracil; F-19 MR imaging; cancer theranostics
资金
- National Natural Science Foundation of China [21675043, 21890744, 51872088, 21804039, 21977027]
- Fundamental Research Funds for the Central Universities, Shenzhen Science and Technology Program [JCYJ20210324140205013]
- Opening Fund of Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research
In this study, zinc-fluorouracil metallodrug networks (Zn-Fu MNs) were designed to enhance immune activity and ROS production. Zn-Fu MNs were found to respond to acidity and ATP, releasing fluorouracil and zinc ions to induce ferroptosis in cancer cells. The synergistic effect of DNA damage and ferroptosis promoted immunogenic cell death and immune cell activation.
Rationale: Ferroptosis drugs inducing cancer immunogenic cell death (ICD) have shown the potential of immunotherapy in vivo. However, the current ferroptosis drugs usually induce the insufficient immune response because of the low ROS generation efficiency. Methods: Herein, we design zinc-fluorouracil metallodrug networks (Zn-Fu MNs), by coordinating Zn and Fu via facile one-pot preparation, to inactivate mitochondria! electron transport for enhanced ROS production and immune activation. Results: Zn-Fu MNs can be responsive toward acidity and adenosine triphosphate (ATP) with the release of Fu and Zn2+, during which Zn2+ can induce mitochondrion disruption to produce ROS, resulting in ferroptosis of cancer cells and 5-Fu interferes with DNA synthesis in nuclei with F-19-MRI signal to be switched on for correlating drug release. With the synergistic effect of DNA damage and ferroptosis, the cancer cells are forced to promote ICD. Thereby, Zn-Fu MNs exhibit the excellent immune response without any other antigens loading. As a result, the infiltration of T cells within tumor and activation of immune cells in spleen have been greatly enhanced. Conclusions: Combined DNA damage and ferroptosis, Zn-Fu MNs induce the violent emission of tumor associated antigens within cancer cells which will sensitize naive dendritic cells and promote the activation and recruitment of cytotoxic T lymphocytes to exterminate cancer cells. Therefore, the obtained Zn-Fu MNs as ferroptosis inducers can effectively remodel immunosuppressive tumor microenvironment and activate antitumor immune reaction.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据