A Glucose/Oxygen-Exhausting Nanoreactor for Starvation- and Hypoxia-Activated Sustainable and Cascade Chemo-Chemodynamic Therapy

被引:231
作者
Guo, Yuxin [1 ]
Jia, Hao-Ran [1 ]
Zhang, Xiaodong [1 ]
Zhang, Xinping [1 ]
Sun, Qing [1 ]
Wang, Shao-Zhe [1 ]
Zhao, Jing [2 ]
Wu, Fu-Gen [1 ]
机构
[1] Southeast Univ, State Key Lab Bioelect, Sch Biol Sci & Med Engn, Nanjing 210096, Peoples R China
[2] Southeast Univ, Sch Med, Inst Neurobiol, Nanjing 210096, Peoples R China
基金
中国国家自然科学基金;
关键词
albumin nanoparticles; hypoxia-activated cancer therapy; metal ion interference therapy; metal-phenolic networks; tumor microenvironment; TARGETED STARVATION; HYDROGEN-PEROXIDE; CANCER STARVATION; NANOPARTICLES;
D O I
10.1002/smll.202000897
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Fenton reaction-mediated chemodynamic therapy (CDT) can kill cancer cells via the conversion of H(2)O(2)to highly toxic HO center dot. However, problems such as insufficient H(2)O(2)levels in the tumor tissue and low Fenton reaction efficiency severely limit the performance of CDT. Here, the prodrug tirapazamine (TPZ)-loaded human serum albumin (HSA)-glucose oxidase (GOx) mixture is prepared and modified with a metal-polyphenol network composed of ferric ions (Fe3+) and tannic acid (TA), to obtain a self-amplified nanoreactor termed HSA-GOx-TPZ-Fe3+-TA (HGTFT) for sustainable and cascade cancer therapy with exogenous H(2)O(2)production and TA-accelerated Fe3+/Fe(2+)conversion. The HGTFT nanoreactor can efficiently convert oxygen into HO center dot for CDT, consume glucose for starvation therapy, and provide a hypoxic environment for TPZ radical-mediated chemotherapy. Besides, it is revealed that the nanoreactor can significantly elevate the intracellular reactive oxygen species content and hypoxia level, decrease the intracellular glutathione content, and release metal ions in the tumors for metal ion interference therapy (also termed "ion-interference therapy" or "metal ion therapy"). Further, the nanoreactor can also increase the tumor's hypoxia level and efficiently inhibit tumor growth. It is believed that this tumor microenvironment-regulable nanoreactor with sustainable and cascade anticancer performance and excellent biosafety represents an advance in nanomedicine.
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页数:9
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