A MXene-Based Bionic Cascaded-Enzyme Nanoreactor for Tumor Phototherapy/Enzyme Dynamic Therapy and Hypoxia-Activated Chemotherapy.
A MXene-Based Bionic Cascaded-Enzyme Nanoreactor for Tumor Phototherapy/Enzyme Dynamic Therapy and Hypoxia-Activated Chemotherapy.
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DOI：
10.1007/s40820-021-00761-w
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发表时间：
2021-12-09
影响因子：
26.6
通讯作者：
Liu J
中科院分区：
文献类型：
--
作者：
Zhang X;Cheng L;Lu Y;Tang J;Lv Q;Chen X;Chen Y;Liu J
通过阻断CD47免疫检查点，实现CD47过表达的基因工程肿瘤细胞膜，提高巨噬细胞介导的肿瘤细胞吞噬作用。提出了一种结合肿瘤酶动力学治疗、光疗和脱氧活化化疗的级联酶纳米反应器。葡萄糖氧化酶和氯过氧化物酶能产生足够的HClO杀死常氧肿瘤细胞，随后激活替拉帕嗪杀死缺氧肿瘤细胞。在线版本包含补充材料，可在10.1007/s40820-021-00761-w获得。酶介导的肿瘤部位活性氧（ROS）的升高已经成为调节细胞内氧化还原状态的抗癌治疗的新兴策略。在此，我们提出了一种基于Ti3C2纳米片的伪装仿生级联酶纳米反应器，用于联合肿瘤酶动力学治疗（EDT）、光疗和脱氧活化化疗。简单地说，将葡萄糖氧化酶（GOX）和氯过氧化物酶（CPO）化学偶联到Ti3C2纳米片上，其中还装载脱氧活化药物替拉帕胺（TPZ），并将Ti3C2-GOX-CPO/TPZ （TGCT）嵌入到具有高表达CD47 （meTGCT）的纳米癌细胞来源的膜泡中。由于具有仿生膜伪装和CD47的过表达，meTGCT具有优越的免疫逃逸和同源靶向能力，可有效增强肿瘤的优先靶向和内化能力。一旦进入肿瘤细胞，GOX和CPO的级联反应可以产生HClO，实现高效EDT。同时，额外的激光照射可以加速酶催化反应速率，增加单线态氧（1O2）的生成。此外，EDT缺氧的局部缺氧环境会激活脱氧敏感的前药进行额外的化疗。因此，meTGCT表现出肿瘤光疗、EDT和化疗的增强协同治疗作用，以有效抑制肿瘤。这种智能级联酶纳米反应器为实现同步和显著的抗肿瘤治疗提供了一种有前途的方法。在线版本包含补充材料，可在10.1007/s40820-021-00761-w获得。
Gene-engineering tumor cell membrane with CD47 over-expression is achieved to improve the macrophage-mediated phagocytosis of tumor cells by blocking CD47 immune checkpoint. A cascade-enzyme nanoreactor combining tumor enzyme dynamic therapy, phototherapy, and deoxygenation-activated chemotherapy is proposed. Glucose oxidase and chloroperoxidase can generate sufficient HClO to kill normoxic tumor cells, and tirapazamine can be subsequently activated to kill hypoxic tumor cells. The online version contains supplementary material available at 10.1007/s40820-021-00761-w. 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 Ti3C2 nanosheets for combined tumor enzyme dynamic therapy (EDT), phototherapy and deoxygenation-activated chemotherapy. Briefly, glucose oxidase (GOX) and chloroperoxidase (CPO) were chemically conjugated onto Ti3C2 nanosheets, where the deoxygenation-activated drug tirapazamine (TPZ) was also loaded, and the Ti3C2-GOX-CPO/TPZ (TGCT) was embedded into nanosized cancer cell-derived membrane vesicles with high-expressed CD47 (meTGCT). Due to biomimetic membrane camouflage and CD47 overexpression, meTGCT 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 (1O2). Furthermore, local hypoxia environment with the oxygen depletion by EDT would activate deoxygenation-sensitive prodrug for additional chemotherapy. Consequently, meTGCT 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. The online version contains supplementary material available at 10.1007/s40820-021-00761-w.
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影响因子：
82.9
作者：
Liu X;Pu Y;Cron K;Deng L;Kline J;Frazier WA;Xu H;Peng H;Fu YX;Xu MM
通讯作者：
Xu MM
热敏外泌体-脂质体混合纳米颗粒介导的化学免疫疗法可改善转移性腹膜癌的治疗
DOI：
10.1002/advs.202000515
发表时间：
2020-09
期刊：
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
影响因子：
--
作者：
Lv Q;Cheng L;Lu Y;Zhang X;Wang Y;Deng J;Zhou J;Liu B;Liu J
通讯作者：
Liu J
用于靶向肿瘤饥饿和脱氧激活化疗且无全身毒性的纳米簇级联酶
影响因子：
17.1
作者：
Ma, Yinchu;Zhao, Yangyang;Wang, Jun
通讯作者：
Wang, Jun
基于白蛋白的治疗诊断纳米药物的光触发保留和级联治疗可减轻肿瘤适应性治疗耐受性
影响因子：
19
作者：
Chen, Jing;Liu, Lu;Liang, Xing-Jie
通讯作者：
Liang, Xing-Jie
二维 MXene 的表面纳米孔工程用于肝细胞癌的靶向协同多疗法
影响因子：
29.4
作者：
Li, Zhenli;Zhang, Han;Yang, Tian
通讯作者：
Yang, Tian