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Biomimetic nanoscale metal–organic framework harnesses hypoxia for effective cancer radiotherapy and immunotherapy
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 hypox...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society of Chemistry
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159451/ https://www.ncbi.nlm.nih.gov/pubmed/34094142 http://dx.doi.org/10.1039/d0sc01949f |
Sumario: | 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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