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ZIF‐Based Nanoparticles Combine X‐Ray‐Induced Nitrosative Stress with Autophagy Management for Hypoxic Prostate Cancer Therapy
Author(s) -
Li Yanli,
Gong Teng,
Gao Hongbao,
Chen Yang,
Li Huiyan,
Zhao Peiran,
Jiang Yaqin,
Wang Kun,
Wu Yelin,
Zheng Xiangpeng,
Bu Wenbo
Publication year - 2021
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202103015
Subject(s) - prostate cancer , autophagy , cancer research , reactive oxygen species , chemistry , apoptosis , cancer cell , hypoxia (environmental) , cancer , oxidative stress , sonodynamic therapy , in vivo , internalization , biophysics , microbiology and biotechnology , medicine , biochemistry , cell , biology , oxygen , organic chemistry
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 (NO 2 − ) 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 Zn 2+ 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 NO 2 − , which inhibits autophagy and further elevates lethal nitrosative stress levels. In addition, dissociated Zn 2+ 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.