TY - JOUR TI - ZIF-Based Nanoparticles Combine X-Ray-Induced Nitrosative Stress with Autophagy Management for Hypoxic Prostate Cancer Therapy AU - Li, Yanli AU - Gong, Teng AU - Gao, Hongbao AU - Chen, Yang AU - Li, Huiyan AU - Zhao, Peiran AU - Jiang, Yaqin AU - Wang, Kun AU - Wu, Yelin AU - Zheng, Xiangpeng AU - Bu, Wenbo T2 - Angewandte Chemie International Edition AB - 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 not only can consume GSH under hypoxia but can 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. DO - https://doi.org/10.1002/anie.202103015 DP - Wiley Online Library VL - n/a IS - n/a LA - en SN - 1521-3773 UR - https://onlinelibrary.wiley.com/doi/abs/10.1002/anie.202103015 Y2 - 2021/05/14/17:44:23 KW - Electrophilic zeolitic imidazole frameworks KW - Low-energy electrons KW - Nitrite (NO2-) KW - Nitrosative stress KW - autophagy ER -