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

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.

• Authors: Kaiyuan Ni, Guangxu Lan, Yang Song, Ziyang Hao, Wenbin Lin
• Journal: Chemical science (Chem Sci) Vol. 11 Issue 29 Pg. 7641-7653 (Apr 20 2020) ISSN: 2041-6520 [Print] England
• PMID: 34094142 (Publication Type: Journal Article)
• Copyright: This journal is © The Royal Society of Chemistry.