A MXene-Based Bionic Cascaded-Enzyme Nanoreactor for Tumor Phototherapy/Enzyme Dynamic Therapy and Hypoxia-Activated Chemotherapy  

作　　者：Xiaoge Zhang Lili Cheng Yao Lu Junjie Tang Qijun Lv Xiaomei Chen You Chen Jie Liu 

机构地区：[1]School of Biomedical Engineering,Shenzhen Campus of Sun Yat-Sen University,No.66,Gongchang Road,Guangming District,Shenzhen,Guangdong 518107,People’s Republic of China [2]Department of General Surgery,The Third Affiliated Hospital of Sun Yat-Sen University,Guangzhou,Guangdong 510006,People’s Republic of China

出　　处：《Nano-Micro Letters》2022年第2期24-44,共21页纳微快报（英文版）

基　　金：This work was supported by the National Natural Science Foundation of China(51773231);Shenzhen Science and Technology Project(JCYJ20190807160801664);the Project of Key Laboratory of Sensing Technology and Biomedical Instruments of Guangdong Province(2011A060901013).

摘　　要：The enzyme-mediated elevation of reactive oxygen species(ROS)at the tumor sites has become an emerging strategy for regulating intracellular redox status for anticancer treatment.Herein,we proposed a camouflaged bionic cascaded-enzyme nanoreactor based on Ti_(3)C_(2)nanosheets for combined tumor enzyme dynamic therapy(EDT),phototherapy and deoxygenation-activated chemotherapy.Briefly,glucose oxidase(GOX)and chloroperoxidase(CPO)were chemically conjugated onto Ti_(3)C_(2)nanosheets,where the deoxygenation-activated drug tirapazamine(TPZ)was also loaded,and the Ti_(3)C_(2)-GOX-CPO/TPZ(TGCT)was embedded into nanosized cancer cell-derived membrane vesicles with high-expressed CD47(m_eTGCT).Due to biomimetic membrane camouflage and CD47 overexpression,m_eTGCT exhibited superior immune escape and homologous targeting capacities,which could effectively enhance the tumor preferential targeting and internalization.Once internalized into tumor cells,the cascade reaction of GOX and CPO could generate HClO for efficient EDT.Simultaneously,additional laser irradiation could accelerate the enzymic-catalytic reaction rate and increase the generation of singlet oxygen(~1O_(2)).Furthermore,local hypoxia environment with the oxygen depletion by EDT would activate deoxygenation-sensitive prodrug for additional chemotherapy.Consequently,m_eTGCT exhibits amplified synergistic therapeutic effects of tumor phototherapy,EDT and chemotherapy for efficient tumor inhibition.This intelligent cascaded-enzyme nanoreactor provides a promising approach to achieve concurrent and significant antitumor therapy.

关 键 词：Cascaded-enzyme nanoreactor Deoxygenation-sensitive prodrugs Tumor enzyme dynamic therapy Phototherapy CD47 

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