Immunogenic radiation therapy for enhanced anti-tumor immunity via core-shell nanocomposite-mediated multiple strategies

被引:6
|
作者
Huang, Naihan [1 ]
Qian, Along [1 ]
Zou, Yiming [1 ]
Lin, Miaoli [1 ]
Pan, Weilun [1 ]
Chen, Ming [1 ]
Meng, Wei [1 ]
Zhang, Wenhua [2 ]
Chen, Jinxiang [1 ]
机构
[1] Southern Med Univ, Sch Pharmaceut Sci, Guangdong Prov Key Lab New Drug Screening, Guangzhou Key Lab Drug Res Emerging Virus Prevent, Guangzhou 510515, Guangdong, Peoples R China
[2] Soochow Univ, Coll Chem Chem Engn & Mat Sci, Suzhou 215123, Peoples R China
来源
THERANOSTICS | 2023年 / 13卷 / 12期
基金
中国国家自然科学基金;
关键词
radiation therapy; tumor microenvironment; anti -tumor immunity; immunogenic cell death; METAL-ORGANIC FRAMEWORKS; CELL-CYCLE ARREST; BREAST-CANCER; TUMOR; MECHANISMS; HYPOXIA; FERROPTOSIS; DOXORUBICIN; METASTASIS; RESISTANCE;
D O I
10.7150/thno.84500
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Background: Due to the immunosuppressive tumor microenvironment (TME), radiation therapy (RT)-mediated immune response is far from satisfactory. How to improve the efficacy of immunogenic RT by priming strong immunogenic cell death (ICD) is an interesting and urgent challenge.Methods: A polyacrylic acid-coated core-shell UiO@Mn3O4 (denoted as UMP) nanocomposite is constructed for immunogenic RT via multiple strategies.Results: Reshaping the TME via Mn3O4-mediated integration of O2 production, GSH depletion, ROS generation and cell cycle arrest, accompanied by Hf-based UiO-mediated radiation absorption, eventually amplifies UMP-mediated RT to induce intense ICD. With the potent ICD induction and reprogrammed tumor-associated macrophages, this synergetic strategy can promote dendritic cells maturation and CD8+ T cells infiltration, and potentiate anti-tumor immunity against primary, distant, and metastatic tumors. Conclusion: This work is expected to shed light on the immunosuppressive TME-reshaping via multiple strategies to reinforce the immunogenic RT outcome and facilitate the development of effective cancer nanomedicine.
引用
收藏
页码:4121 / 4137
页数:17
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