ZIF‐Based Nanoparticles Combine X‐Ray‐Induced Nitrosative Stress with Autophagy Management for Hypoxic Prostate Cancer Therapy

Abstract

Although reactive oxygen species (ROS)-mediated tumor treatments are predominant in clinical applications, ROS-induced protective autophagy promotes cell survival, especially in hypoxic tumors.H erein, X-ray triggered nitrite (NO 2 À )i su sed for hypoxic prostate cancer therapyb y inhibiting autophagy and inducing nitrosative stress based on an electrophilic zeolitic imidazolef ramework (ZIF-82-PVP). After internalization of pH-responsive ZIF-82-PVP nanoparticles,e lectrophilic 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 À ,w hich inhibits autophagy and further elevates lethal nitrosative stress levels.I na ddition, dissociated Zn 2+ specifically limits the migration and invasion of prostate cancer cells through ion interference.I nvitro and in vivo results indicate that ZIF-82-PVP nanoparticles under X-ray irradiation can effectively promote the apoptosis of hypoxic prostate cancer cells.O verall, this nitrosative stressmediated tumor therapys trategy provides an ovel approach targeting hypoxic tumors.

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