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Acta Biomaterialia · 2021 · IF 8.947

Biodegradable BiOCl platform for oxidative stress injury–enhanced chemodynamic/radiation therapy of hypoxic tumors

Yongtian Liu,Jing Zhang,Jun Du,Kang Song,Jinliang Liu,Xiang Wang,Bing Li,Ruizhuo Ouyang,Yuqing Miao,Yun Sun,Yuhao Li

Various physiological characteristics of the tumor microenvironment (TME), such as hypoxia, overexpression of glutathione (GSH) and hydrogen peroxide (H 2 O 2 ), and mild acidity, can severely reduce the efficacy of many cancer therapies. Altering the redox balance of the TME and increasing oxidative stress can accordingly enhance the efficacy of tumor therapy. Herein, we developed a bismuth-based Cu 2+ -doped BiOCl nanotherapeutic platform, BCHN, able to self-supply H 2 O 2 for TME-regulated chemodynamic therapy (CDT) combined with sensitized radiotherapy (RT). BCHN released H 2 O 2 and consumed GSH to degrade the composite in the slightly acidic TME, and generated hydroxyl radicals (•OH) via a Fenton-like reaction catalyzed by copper ions , to achieve oxidative stress-enhanced CDT. The Fenton-like reaction also catalyzed H 2 O 2 to produce O 2 to relieve tumor hypoxia , and combined with the X-ray-blocking property of bismuth to realize TME-enhanced radiotherapy. Synergistic CDT/RT has previously been shown to effectively inhibit tumor cell proliferation and achieve effective tumor control. The current results demonstrated a highly efficient multifunctional bio-degradable nanoplatform for oncotherapy. Statement of significance Tumor microenvironment-modulated synergy of radiotherapy and chemodynamic therapy is conducive to rapid tumor ablation. Based on this principle, we fabricated a biodegradable BiOCl-based nanocomposite , BCHN. By supplying H 2 O 2 , a Fenton-like reaction generated •OH and O 2 catalyzed by copper ions, and consumed glutathione to biodegrade the composite. Overall, these actions increased tumor oxidative stress and realized the synergistic anti-tumor actions of chemodynamic therapy combined with bismuth-based sensitization radiotherapy . This strategy thus provides a unique approach to oncology therapy.

研究领域: 肿瘤学 · 纳米医学 · 生物材料学
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