期刊
CHEMICAL SCIENCE
卷 11, 期 29, 页码 7641-7653出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/d0sc01949f
关键词
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资金
- National Cancer Institute [U01-CA198989]
- Department of Defense [PC170934P2]
- University of Chicago Medicine Comprehensive Cancer Center (NIH) [CCSG: P30 CA014599]
- Ludwig Institute for Metastasis Research
Tumor hypoxia presents a major impediment to effective cancer therapy with ionizing radiation and immune checkpoint inhibitors. Here we report the design of a biomimetic nanoscale metal-organic-framework (nMOF), Hf-DBP-Fe, with catalase-like activity to decompose elevated levels of H(2)O(2)in hypoxic tumors to generate oxygen and hydroxyl radical. The generated oxygen attenuates hypoxia to enable radiodynamic therapy upon X-ray irradiation and fixes DNA damage while hydroxyl radical inflicts direct damage to tumor cells to afford chemodynamic therapy. Hf-DBP-Fe thus mediates effective local therapy of hypoxic cancer with low-dose X-ray irradiation, leading to highly immunogenic tumor microenvironments for synergistic combination with anti-PD-L1 immune checkpoint blockade. This combination treatment not only eradicates primary tumors but also rejects distant tumors through systemic anti-tumor immunity. We have thus advanced an nMOF-based strategy to harness hypoxic tumor microenvironments for highly effective cancer therapy using a synergistic combination of low dose radiation and immune checkpoint blockade.
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