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Perfluorooctyl bromide nanoemulsions holding MnO_(2) nanoparticles with dual-modality imaging and glutathione depletion enhanced HIFU-eliciting tumor immunogenic cell death

查看全文 作　　者：Xinping [1]Kuai;Yuefei [2]Zhu;Zheng [3]Yuan;Shengyu [4]Wang;Lin [1]Lin;Xiaodan [5]Ye;Yiping [1]Lu;Yu [6]Luo;Zhiqing [2]Pang;Daoying [1]Geng;Bo [1]Yin 高影响力作者 机构地区：[1]Department of Radiology,Huashan Hospital,Fudan University,Shanghai 200040,China;[2]School of Pharmacy,Fudan University,Key Laboratory of Smart Drug Delivery,Ministry of Education,Shanghai 201203,China;[3]Department of Radiology,Shanghai First Maternity and Infant Hospital,Tongji University School of Medicine,Shanghai 201204,China;[4]Department of Radiology,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 201800,China;[5]Department of Radiology,Shanghai Chest Hospital,Shanghai Jiao Tong University,Shanghai 200030,China;[6]State Key Laboratory of High Performance Ceramics and Superfine Microstructure,School of Chemical Science and Engineering,Shanghai 200092,China高影响力机构 出　　处：《Acta Pharmaceutica Sinica B》索引2022年第12卷第2期,共15页高影响力期刊 基　　金：supported by Shanghai Municipal Science and Technology Major Project(No.2018SHZDZX01,China);ZJ Lab,Shanghai Natural Science Foundation(Grant No.18ZR1405700,China);National Natural Science Foundation of China(Fund Nos.81773283 and 81901697);Shanghai Sailing Program(Grant No.18YF1403000,China);Shanghai Chest Hospital Project of Collaborative Innovation(Grant No.YJXT20190203,China);the Opening Project of State Key Laboratory of High Performance Ceramics and Superfine Microstructure(SKL201908SIC,China)。 摘　　要：Tumor-targeted immunotherapy is a remarkable breakthrough,offering the inimitable advantage of specific tumoricidal effects with reduced immune-associated cytotoxicity.However,existing platforms suffer from low efficacy,inability to induce strong immunogenic cell death(ICD),and restrained capacity of transforming immune-deserted tumors into immune-cultivated ones.Here,an innovative platform,perfluorooctyl bromide(PFOB)nanoemulsions holding MnO_(2) nanoparticles(MBP),was developed to orchestrate cancer immunotherapy,serving as a theranostic nanoagent for MRI/CT dual-modality imaging and advanced ICD.By simultaneously depleting the GSH and eliciting the ICD effect via highintensity focused ultrasound(HIFU)therapy,the MBP nanomedicine can regulate the tumor immune microenvironment by inducing maturation of dendritic cells(DCs)and facilitating the activation of CD8^(+)and CD4^(+)T cells.The synergistic GSH depletion and HIFU ablation also amplify the inhibition of tumor growth and lung metastasis.Together,these findings inaugurate a new strategy of tumor-targeted immunotherapy,realizing a novel therapeutics paradigm with great clinical significance. 关 键 词：Immunogenic cell death NANOEMULSIONS Manganese dioxide nanoparticles Glutathione depletion Dual-modality imaging High-intensity focused ultrasound Tumor microenvironment
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