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A covalent organic framework-based multifunctional therapeutic platform for enhanced photodynamic therapy via catalytic cascade reactions

一种基于共价有机框架的多功能治疗平台通过催化级联反应增强光动力治疗

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Abstract

Utilizing the unique tumor microenvironment (TME) to conduct chemical reactions for cancer treatment becomes a hot topic recently. Nevertheless, single chemical reaction in TME is often restricted by scanty reaction substrates and slow reaction rate. Meanwhile, the toxic substances produced by the reactions are usually not enough to kill cancer cells. Herein, using covalent organic frameworks (COFs) as the template, Au nanoparticles (Au NPs) were subsequently grown on the surface of the COF, then a thin layer of manganese dioxide (MnO2) was coated over the material, and finally hyaluronic acid (HA) was introduced to improve the biocompatibility. The resultant product, named COF-Au-MnO2, was involved in several processes to form cascade reactions in the TME. Specifically, under hypoxic conditions, COF-Au-MnO2 could react with intratumoral H2O2 to produce O2 to enhance the type II photodynamic therapy (PDT), and Au NPs could decompose glucose to promote starving-like therapy. Besides, starving-like therapy can also produce H2O2 to increase O2 production. Simultaneously, MnO2 can consume glutathione (GSH) to enhance the antitumor efficacy, and the released Mn2+ could be used for T1-weighted magnetic resonance imaging (MRI). Both in vitro and in vivo experiments had proven excellent cancer cell killing effect and antitumor efficacy of COF-Au-MnO2via such a cycle-like process.

摘要

近年来, 利用肿瘤独特的微环境进行肿瘤治疗成为了热门研究话题, 然而这种治疗方法经常受到诸多条件的限制, 如较少的反应底物和较慢的反应速率, 反应所产生的毒性物质也不足以杀死癌细胞等. 本文以共价有机骨架(COFs)为模板, 在表面生长金纳米颗粒, 然后再包覆一层二氧化锰, 最后用透明质酸修饰以提高材料的生物相容性. 最终得到的产物可以在肿瘤微环境中形成级联反应: 在缺氧条件下, 二氧化锰可以分解肿瘤内部的过氧化氢产生氧气以增强II型光动力疗法; 金纳米颗粒可以通过分解葡萄糖用于饥饿疗法, 同时, 饥饿疗法所产生的过氧化氢又可以促进氧气的生成. 此外, 肿瘤内部的谷胱甘肽可以将二氧化锰分解为二价锰离子, 而二价锰离子可以用于T1加权MR成像. 最终体内和体外实验证明, 该复合材料具有良好的癌细胞杀伤能力和抗肿瘤效果.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (21471145), the Science and Technology Development Planning Project of Jilin Province (20170101179JC), and the “Hundred Talents Program” of Chinese Academy of Sciences.

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Authors and Affiliations

  1. State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China

    Lihan Cai  (蔡砺寒), Chunling Hu  (胡春玲), Sainan Liu  (刘赛男), Ying Zhou  (周莹), Maolin Pang  (逄茂林) & Jun Lin  (林君)

  2. University of Science and Technology of China, Hefei, 230026, China

    Lihan Cai  (蔡砺寒), Chunling Hu  (胡春玲), Sainan Liu  (刘赛男), Maolin Pang  (逄茂林) & Jun Lin  (林君)

  3. School of Applied Physics and Materials, Wuyi University, Jiangmen, 529020, China

    Jun Lin  (林君)

Authors
  1. Lihan Cai  (蔡砺寒)
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  6. Jun Lin  (林君)
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Contributions

Author contributions Pang M put forward the research ideas. Cai L performed the experiments. Hu C, Liu S and Zhou Y performed part of the experiments. Cai L wrote the paper with support from Pang M and Lin J. All authors contributed to the general discussion.

Corresponding authors

Correspondence to Maolin Pang  (逄茂林) or Jun Lin  (林君).

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

Additional information

Lihan Cai is a master candidate at the University of Science and Technology of China. His current research focuses on the controllable preparation of covalent organic framework and its biomedical application.

Maolin Pang obtained his BSc degree from the Northeast Normal University in 2000 and PhD degree from Changchun Institute of Applied Chemistry (CIAC), Chinese Academy of Sciences (CAS), in 2005. After graduation, he worked as postdoctoral fellow at Osaka University (JSPS), National University of Singapore, and King Abdullah University of Science and Technology, respectively. In 2014, he joined CIAC as a full professor, and was selected as a member of the “Hundred Talents Program” of the CAS in 2015. His research mainly focuses on the synthesis of micro- or nano-sized porous materials and investigation of their potential application in catalysis and biomedical fields.

Jun Lin received his BSc and MSc degrees in inorganic chemistry from Jilin University in 1989 and 1992, respectively, and a PhD degree (inorganic chemistry) from CIAC, CAS, in 1995. He worked as a postdoctoral researcher for more than 4 years at the City University of Hong Kong (1996), Institute of New Materials (Germany, 1997), Virginia Commonwealth University (USA, 1998), and University of New Orleans (USA, 1999). He is a professor at CIAC, CAS. His research interests include luminescent materials and multifunctional composite materials toward their applications in display, lighting and biomedical fields.

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A covalent organic framework based multifunctional therapeutic platform for enhanced photodynamic therapy via a catalytic cascade reaction

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Cai, L., Hu, C., Liu, S. et al. A covalent organic framework-based multifunctional therapeutic platform for enhanced photodynamic therapy via catalytic cascade reactions. Sci. China Mater. 64, 488–497 (2021). https://doi.org/10.1007/s40843-020-1428-0

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