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

被引：11

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

页码：4121 / 4137

页数：17

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[1] Systematic review of case reports on the abscopal effect [J].