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作者

Wen Zhao Jintao Du Yunxuan Song Zilin Ma Songyan Li Yuhua Wei Guiqiang Zhang

作者单位

²Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong 250117, China ¹Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, China

刊名

Ultrasonics Sonochemistry

年份

2025

页码

107680

ISSN

1350-4177

关键词

Sonodynamic therapy Glutamine metabolism Redox homeostasis Immunosuppressive tumor microenvironment

摘要

The immunotherapeutic potential of sonodynamic therapy is hindered by tumor defense mechanisms driven by glutamine metabolism, including glutathione -dependent redox homeostasis and an immunosuppressive tumor microenvironment . To address these challenges, we herein developed metabolic nanoblockers by encapsulating a glutamine metabolism inhibitor CB839 and a sonosensitizer chlorin e6 into melanin-inspired nanoparticles. The resulting nanoblockers triggered robust reactive oxygen species pro...更多

The immunotherapeutic potential of sonodynamic therapy is hindered by tumor defense mechanisms driven by glutamine metabolism, including glutathione -dependent redox homeostasis and an immunosuppressive tumor microenvironment . To address these challenges, we herein developed metabolic nanoblockers by encapsulating a glutamine metabolism inhibitor CB839 and a sonosensitizer chlorin e6 into melanin-inspired nanoparticles. The resulting nanoblockers triggered robust reactive oxygen species production upon ultrasound irradiation, thereby destroying tumor cells and inducing immunogenic cell death . Concurrently, they inhibited the glutamine metabolism in the tumor, disrupting redox homeostasis and remodeling the immunosuppressive TME, thereby amplifying both SDT-generated oxidative stress and ICD-induced antitumor immunity. CBE@AM NPs demonstrated a potent tumor-inhibitory effect in tumor-bearing mice, highlighting their potential for immunometabolic reprogramming to enhance the therapeutic efficacy of SDT.收起

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