Synergistic enhancement of ultrasound therapy for tumors using hypoxia-activated 6-diazo-5-oxo-L-norleucine(DON)prodrug nanoparticles  

作　　者：Mengfei Zheng Zhilin Liu Hang Xu Daping Ye Linjie Cui Chenguang Yang Lili Ma Kun Wang Kazuo Sakurai Zhaohui Tang 

机构地区：[1]Key Laboratory of Polymer Ecomaterials,Changchun Institute of Applied Chemistry,Chinese Academy of Sciences,Changchun 130022,China [2]School of Applied Chemistry and Engineering,University of Science and Technology of China,Hefei 230026,China [3]Jilin Biomedical Polymers Engineering Laboratory,Changchun 130022,China [4]Department of Chemistry and Biochemistry,The University of Kitakyushu,1-1 Hibikino,Kitakyushu 808-0135,Japan

出　　处：《Nano Research》2024年第7期6323-6331,共9页纳米研究（英文版）

基　　金：financially supported by the Ministry of Science and Technology of China(No.2022YFE0110200);the Natural Science Foundation of Jilin Province(No.20230101037JC);the National Natural Science Foundation of China(Nos.52203198 and 52025035).

摘　　要：Ultrasound(US)has been applied in clinical practice for its non-invasive and high selectivity.However,it is difficult to achieve a satisfactory anti-tumor effect with US alone.Meanwhile,the use of US therapy alone can exacerbate tumor hypoxia.In this study,we prepared hypoxia-activated 6-diazo-5-oxo-L-norleucine(DON)prodrug nanoparticles(HDON-NPs)to improve US therapeutic effects.In an H22 murine liver cancer model,US therapy selectively disrupted tumor blood vessels,leading to increased tumor hypoxia and a 1.67-fold increase in the expression of nitroreductase(NTR).The combination therapy of US and HDON-NPs demonstrated a synergistic effect,resulting in a tumor suppression rate(TSR)of 90.2%±6.4%,which was 5.93-fold higher than that of US therapy alone.The combined treatment selectively blocked the glutamine metabolism of the tumor cells while simultaneously activating the T cells in the tumor microenvironment,thereby exerting a robust anti-tumor effect.

关 键 词：ultrasound therapy hypoxia-activated prodrug nanoparticles 6-diazo-5-oxo-L-norleucine(DON) glutamine antagonist starvation therapy 

分 类 号：R730.5[医药卫生—肿瘤] TB383.1[医药卫生—临床医学]