期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 60, 期 28, 页码 15472-15481出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202103015
关键词
autophagy; electrophilic zeolitic imidazole frameworks; low-energy electrons; nitrite; nitrosative stress
资金
- National Funds for Distinguished Young Scientists [51725202]
- Key Project of Shanghai Science and Technology Commission [19JC1412000]
- National Natural Science Foundation of China [51872094, 21805090, 22005271]
- National Key R&D Program of China [2018YFA0107900]
- Collaborative Innovation Center of Technology and Equipment for Biological Diagnosis and Therapy in Universities of Shandong
The ZIF-82-PVP nanoparticles can effectively promote apoptosis of hypoxic prostate cancer cells under X-ray irradiation by inhibiting autophagy and inducing nitrosative stress.
Although reactive oxygen species (ROS)-mediated tumor treatments are predominant in clinical applications, ROS-induced protective autophagy promotes cell survival, especially in hypoxic tumors. Herein, X-ray triggered nitrite (NO2-) is used for hypoxic prostate cancer therapy by inhibiting autophagy and inducing nitrosative stress based on an electrophilic zeolitic imidazole framework (ZIF-82-PVP). After internalization of pH-responsive ZIF-82-PVP nanoparticles, electrophilic ligands and Zn2+ are delivered into cancer cells. Electrophilic ligands can not only consume GSH under hypoxia but also capture low-energy electrons derived from X-rays to generate NO2-, which inhibits autophagy and further elevates lethal nitrosative stress levels. In addition, dissociated Zn2+ specifically limits the migration and invasion of prostate cancer cells through ion interference. In vitro and in vivo results indicate that ZIF-82-PVP nanoparticles under X-ray irradiation can effectively promote the apoptosis of hypoxic prostate cancer cells. Overall, this nitrosative stress-mediated tumor therapy strategy provides a novel approach targeting hypoxic tumors.
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