Starvation-Sensitized and Oxygenation-Promoted Tumor Sonodynamic Therapy by a Cascade Enzymatic Approach

作     者：Wencheng Wu Yinying Pu Han Lin Heliang Yao Jianlin Shi Wencheng Wu;Yinying Pu;Han Lin;Heliang Yao;Jianlin Shi

作者机构：The State Key Lab of High Performance Ceramics and Superfine MicrostructuresShanghai Institute of CeramicsChinese Academy of SciencesShanghai 200050China Center of Materials Science and Optoelectronics EngineeringUniversity of Chinese Academy of SciencesBeijing 100049China Department of Medical UltrasoundShanghai Tenth People’s HospitalUltrasound Research and Education InstituteTongji University School of MedicineShanghai 200072China Platform of Nanomedicine TranslationShanghai Tenth People’s Hospital of Tongji UniversityShanghai 200072China 

出 版 物：《Research》 (研究（英文）)

年 卷 期：2021年第2021卷第1期

页      面：763-779页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：the financial support from the Natural Science Foundation of China(21835007) the Project of Shanghai Science and Technology Committee(17JC1404701) 

主　　题：protective dynamic loaded 

摘      要：The therapeutic outcomes of noninvasive sonodynamic therapy(SDT)are always compromised by tumor hypoxia,as well as inherent protective mechanisms of ***,we report a simple cascade enzymatic approach of the concurrent glucose depletion and intratumoral oxygenation for starvation-sensitized and oxygenation-amplified sonodynamic therapy using a dual enzyme and sonosensitizer-loaded nanomedicine designated as GOD/CAT@*** particular,glucose oxidase-(GOD-)catalyzed glycolysis would cut off glucose supply within the tumor,resulting in the production of tumor hydrogen peroxide(H_(2)O_(2))while causing tumor cells *** generated H_(2)O_(2)could subsequently be decomposed by catalase(CAT)to generate oxygen,which acts as reactants for the abundant singlet oxygen(^(1 O_(2))production by loaded sonosensitizer hematoporphyrin monomethyl ether(HMME)upon the US irradiation,performing largely elevated therapeutic outcomes of *** the meantime,the severe energy deprivation enabled by GOD-catalyzed glucose depletion would prevent tumor cells from executing protective mechanisms to defend themselves and make the tumor cells sensitized and succumbed to the cytotoxicity of^(1 O_(2)).Eventually,GOD/CAT@ZPF-Lips demonstrate the excellent tumoral therapeutic effect of SDT in vivo without significant side effect through the cascade enzymatic starvation and oxygenation,and encouragingly,the tumor xenografts have been found completely eradicated in around 4 days by the intravenous injection of the nanomedicine without reoccurrence for as long as 20 days.