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Vol. 14 (2022)

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

https://doi.org/10.1007/s40820-021-00761-w
Xiaoge Zhang
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
Lili Cheng
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
Yao Lu
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
Junjie Tang
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
Qijun Lv
Department of General Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510006, People’s Republic of China
Xiaomei Chen
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
You Chen
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
Jie Liu
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

Corresponding Author: Jie Liu

liujie56@mail.sysu.edu.cn

Nano-Micro Letters, Vol. 14 (2022), Article Number: 22

Abstract

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.


Highlights:


1 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.
2 A cascade-enzyme nanoreactor combining tumor enzyme dynamic therapy, phototherapy, and deoxygenation-activated chemotherapy is proposed.
3 Glucose oxidase and chloroperoxidase can generate sufficient HClO to kill normoxic tumor cells, and tirapazamine can be subsequently activated to kill hypoxic tumor cells.

Keywords

Cascaded-enzyme nanoreactor Deoxygenation-sensitive prodrugs Tumor enzyme dynamic therapy Phototherapy CD47
Zhang, Xiaoge, Lili Cheng, Yao Lu, Junjie Tang, Qijun Lv, Xiaomei Chen, You Chen, and Jie Liu. 2021. “A MXene-Based Bionic Cascaded-Enzyme Nanoreactor for Tumor Phototherapy/Enzyme Dynamic Therapy and Hypoxia-Activated Chemotherapy”. Nano-Micro Letters 14 (December):22. https://doi.org/10.1007/s40820-021-00761-w.
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