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Covalent organic framework-based nanozyme for cascade-amplified synergistic cancer therapy

基于共价有机框架的纳米酶用于级联放大反应协同治疗癌症

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Abstract

Due to the limited concentration of hydrogen peroxide (H2O2) in the tumor microenvironment, peroxidase (POD)-mimicking nanozyme-mediated catalytic therapy usually cannot completely eliminate tumor issues. In this study, we report an H2O2-responsive nanozyme constructed by loading 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) into POD-like Fe-porphyrin covalent organic frameworks (COFs) (Fe-DhaTph). The resulting ABTS@Fe-DhaTph can function as a multifunctional therapeutic nanoagent for combination therapy of catalytic therapy, photothermal therapy (PTT), and photodynamic therapy (PDT). In the tumor microenvironment, ABTS@Fe-DhaTph can catalyze the decomposition of endogenous H2O2 to produce highly cytotoxic hydroxyl radicals (·OH) for in situ tumor catalytic therapy. Meanwhile, the loaded ABTS is oxidized by H2O2 with the assistance of ABTS@Fe-DhaTph, and the resulting oxABTS, with strong near-infrared absorbance, can enable the H2O2-dependent PTT. Besides Fe-DhaTph-induced PDT, the generated oxABTS with glutathione (GSH)-depletion ability can synergistically enhance the generation of reactive oxygen species, thereby improving catalytic therapy and PDT. To the best of our knowledge, ABTS@Fe-DhaTph is the first COF-based nanozyme to serve as a cascade-amplified synergistic therapeutic nanoagent for cancer treatment.

摘要

在肿瘤微环境中, 过氧化氢(H2O2)的浓度受限, 导致模拟过氧化物酶(POD)介导的单一催化治疗无法完全消除肿瘤. 为了克服这个问题, 我们将2,2′-氮基-双(3-乙基苯并噻唑-6-磺酸) (ABTS)负载到具有模拟过氧化物酶活性的铁卟啉基共价有机框架(Fe-DhaTph)上, 从而构建了H2O2响应型纳米酶ABTS@Fe-DhaTph. 这种纳米酶是一种多功能纳米治疗剂, 可以实现催化、 光热和光动力联合治疗. 在肿瘤微环境中, ABTS@Fe-DhaTph可以催化内源性H2O2分解, 并产生羟基自由基, 这些自由基可用于肿瘤原位催化治疗. 同时, ABTS在ABTS@Fe-DhaTph的催化作用下被H2O2氧化, 生成具有较强近红外光吸收能力的oxABTS, 从而实现H2O2激活的光热治疗. Fe-DhaTph则可以在660 nm激光照射下实现光动力治疗. 此外, oxABTS还能消耗细胞内谷胱甘肽, 协同提高细胞内活性氧水平, 从而提高催化治疗和光动力治疗效果. 据我们所知, ABTS@Fe-DhaTph是第一个用于级联放大反应协同治疗癌症的COF基纳米酶.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (21971153 and 22371172), the Major Basic Research Projects of Shandong Provincial Natural Science Foundation (ZR2020ZD32), Taishan Scholars Climbing Program of Shandong Province, China Postdoctoral Science Foundation (2020M682225), and the Natural Science Foundation of Shandong Province (ZR202102280580 and ZR202102210262).

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  1. These authors contributed equally to this work.

Authors and Affiliations

  1. College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Normal University, Jinan, 250014, China

    Jie Feng  (冯杰), Fei Kong  (孔斐), Wan-Sheng Yue  (岳万胜), Hao Yu  (于浩), Zi-Liang He  (何梓良), Ya-Nan Zhai  (翟亚男) & Yu-Bin Dong  (董育斌)

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  1. Jie Feng  (冯杰)
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  2. Fei Kong  (孔斐)
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  3. Wan-Sheng Yue  (岳万胜)
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  4. Hao Yu  (于浩)
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Contributions

Author contributions Feng J conceived and designed this work. Kong F, Yu H, Yue WS, He ZL, and Zhai YN performed the synthesis and characterization. Kong F and Yu H performed the test experiments. All authors analyzed the data. Feng J and Dong YB wrote the manuscript. All authors commented on the manuscript.

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Correspondence to Jie Feng  (冯杰) or Yu-Bin Dong  (董育斌).

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Conflict of interest The authors declare that they have no conflict of interest.

Additional information

Jie Feng received her Master’s degree from Shandong Normal University (SDNU) in 2016 and obtained her PhD degree in analytical chemistry from Wuhan University in 2019. In the same year, she joined Prof. Yu-Bin Dong’s group at SDNU. Her current research interest mainly focuses on the rational design and preparation of advanced multifunctional nanomaterials (e.g., MOFs and COFs) for related biomedical applications.

Fei Kong received her Bachelor’s degree in chemistry from Qufu Normal University in 2020. She is currently a Master candidate in Prof. Yu-Bin Dong’s group at SDNU. Her main research focuses on MOF and COF nanomaterials for cancer treatment.

Yu-Bin Dong is a Chang Jiang Scholar of Chemistry at SDNU. He obtained his PhD degree from Nankai University (under Prof. Li-Cheng Song) in 1996. Then, he joined Prof. Andreas Mayr’s group at the University of Hong Kong and Prof. Hans-Conrad zur Loye’s group at the University of South Carolina from 1996 to 2000, and he was promoted as a full professor at SDNU in 2000. His current research interests mainly focus on MOF- and COF-based materials and their applications in catalysis, sensing, bioimaging, and cancer treatment.

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Feng, J., Kong, F., Yue, WS. et al. Covalent organic framework-based nanozyme for cascade-amplified synergistic cancer therapy. Sci. China Mater. 66, 4079–4089 (2023). https://doi.org/10.1007/s40843-023-2560-8

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