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Biomimetic nanoscale metal–organic framework harnesses hypoxia for effective cancer radiotherapy and immunotherapy

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Abstract

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 H2O2 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.

Graphical abstract: Biomimetic nanoscale metal–organic framework harnesses hypoxia for effective cancer radiotherapy and immunotherapy

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Article information


Submitted
04 Apr 2020
Accepted
15 Apr 2020
First published
20 Apr 2020

This article is Open Access
All publication charges for this article have been paid for by the Royal Society of Chemistry

Chem. Sci., 2020, Advance Article
Article type
Edge Article

Biomimetic nanoscale metal–organic framework harnesses hypoxia for effective cancer radiotherapy and immunotherapy

K. Ni, G. Lan, Y. Song, Z. Hao and W. Lin, Chem. Sci., 2020, Advance Article , DOI: 10.1039/D0SC01949F

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