Record-High Ultrasound-Sensitive NO Nanogenerators for Cascade Tumor Pyroptosis and Immunotherapy

被引:14
作者
Bao, Yuheng [1 ]
Ge, Yanni [2 ]
Wu, Mengjie [3 ]
Mao, Zhengwei [1 ]
Ye, Juan [2 ]
Tong, Weijun [1 ]
机构
[1] Zhejiang Univ, Dept Polymer Sci & Engn, MOE Key Lab Macromol Synth & Functionalizat, Minist Educ, Hangzhou 310027, Zhejiang, Peoples R China
[2] Zhejiang Univ, Affiliated Hosp 2, Zhejiang Prov Engn Inst Eye Dis, Eye Ctr, Hangzhou 310009, Zhejiang, Peoples R China
[3] Zhejiang Univ, Canc Ctr, Stomatol Hosp, Zhejiang Prov Clin Res Ctr Oral Dis,Sch Med, Hangzhou 310058, Zhejiang, Peoples R China
基金
中国国家自然科学基金;
关键词
cascade tumor therapy; cGAS-STING; hollow MnO2; NO donor; pyroptosis; ultrasound response; NITRIC-OXIDE; THERAPY; NITROSAMINES; NANOSHEETS; MECHANISM; RELEASE; MNO2; DNA;
D O I
10.1002/advs.202302278
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Pyroptosis is a pro-inflammatory cell death that is associated with innate immunity promotion against tumors. Excess nitric oxide (NO)-triggered nitric stress has potential to induce pyroptosis, but the precise delivery of NO is challenging. Ultrasound (US)-responsive NO production has dominant priority due to its deep penetration, low side effects, noninvasion, and local activation manner. In this work, US-sensitive NO donor N-methyl-N-nitrosoaniline (NMA) with thermodynamically favorable structure is selected and loaded into hyaluronic acid (HA)-modified hollow manganese dioxide nanoparticles (hMnO(2) NPs) to fabricate hMnO(2)@HA@NMA (MHN) nanogenerators (NGs). The obtained NGs have a record-high NO generation efficiency under US irradiation and can release Mn2+ after targeting the tumor sites. Later on, cascade tumor pyroptosis and cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING)-based immunotherapy is achieved and tumor growth is effectively inhibited.
引用
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页数:13
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