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Nature-inspired nanothylakoids for multimodal cancer therapeutics

天然来源的纳米类囊体应用于肿瘤的多模式治疗

Abstract

Multimodal therapy has been recognized as a powerful platform for the precise treatment of cancer. However, the reported multimodal therapeutic systems often involve sophisticated components and tedious fabrication procedures. As such, developing nature-inspired and easily-obtainable theranostic agents for multimodal cancer therapy remains challenging. In this work, we propose nature-inspired nanothylakoids as a multimodal theranostic agent for cancer therapy both in vitro and in vivo. Nanothylakoids extracted from spinach leaves exhibit prominent photothermal and photodynamic inactivation on 4T1 and MCF-7 cancer cells due to their outstanding photothermal conversion/photosensitization capabilities. Additionally, the peroxidase-like catalytic activity of nanothylakoids is simultaneously verified, which facilitates the oxidation of H2O2 to the cytotoxic hydroxyl radical (·OH) and thus cause efficient cell apoptosis. Interestingly, a selective cytotoxicity of nanothylakoids on MCF-7 cancer cells is found due to their overexpression of H2O2. In vitro and in vivo results substantiate the prominent therapeutic outcome and excellent biosafety of nanothylakoids. Nanothylakoids with photothermal/photodynamic effects and peroxidase-like catalytic activity open a new avenue for the development of nature-inspired theranostic materials, holding great promise in multimodal cancer therapeutics.

摘要

多模式联合治疗已成为抗肿瘤的有效手段, 但目前已报道的多模式肿瘤治疗试剂通常需要复杂的功能组分和繁琐的合成过程. 因此, 开发一种简单制备的天然来源多模式肿瘤治疗试剂仍然是一个挑战. 本文从菠菜叶片中提取出了一种天然来源的、 具有类酶性质的纳米类囊体用于肿瘤的多模式治疗. 结果表明, 纳米类囊体具有良好的光热转换和光敏化性质, 可以有效杀伤4T1和MCF-7肿瘤细胞. 同时, 该材料还具有类过氧化物酶的性质, 可以氧化分解过氧化氢产生羟基自由基从而诱导肿瘤细胞凋亡. 因MCF-7肿瘤细胞内过量表达过氧化氢, 该材料可实现对MCF-7肿瘤细胞的选择性杀伤. 该纳米类囊体在细胞水平和活体小动物水平对肿瘤具有显著的治疗效果, 且表现出良好的生物安全性. 研究表明, 该纳米类囊体具有光热转换、 光敏化、 类过氧化物酶的性质, 是一类很有应用前景的多模式肿瘤治疗试剂.

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Acknowledgements

The work was supported by the National Natural Science Foundation of China (22021002, 22020102005, and 22022705) and the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA16020804).

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Authors and Affiliations

Authors

Contributions

Author contributions Huang Y, Lv F, and Wang S designed the research. Zhao H isolated the nanothylakoids and performed the experiments with Guo Y and Yuan A. Zhao H wrote the paper with support from Xia S, Gao Z, and Liu L. All authors contributed to the general discussion.

Corresponding authors

Correspondence to Yiming Huang, Fengting Lv or Shu Wang.

Ethics declarations

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

Additional information

Hao Zhao received his PhD degree from the Institute of Chemistry, Chinese Academy of Sciences (ICCAS). His current research interest mainly focuses on conjugated polymer-nature-inspired bioactive materials for biomedical applications.

Yiming Huang obtained his BSc degree in chemistry from Nanjing University in 2009. He then joined the group of Prof. Dominic V. McGrath at University of Arizona. After completing his PhD in 2015, he worked as a postdoc research associate with Prof. Eilaf Egap at Emory University and Rice University. He joined the ICCAS in 2018. His research focuses on functional polymers for biomedical applications.

Fengting Lv received her BSc, MSc, and PhD degrees from Shaanxi Normal University in 2002, 2005, and 2008, respectively. She spent one year at Michigan State University as a joint PhD student. In 2009, she moved to the Institute of Chemistry, Chinese Academy of Sciences as a postdoctoral fellow in Prof. Wang’s group, and became a professor in 2021. Her current research interest focuses on the design of water-soluble conjugated polymers for bioassembly and bioelectronics applications.

Shu Wang obtained his BSc degree from Hebei University in 1994, and then PhD degree at Peking University in 1999. He worked as a postdoctoral researcher at the IC-CAS from 1999 to 2001, and at the University of California, Santa Barbara from 2001 to 2004. In 2004, he became a full professor at the ICCAS. His current research interests include the design and synthesis of novel conjugated polymers for disease therapeutic, biocatalysis, and organic bioelectronics.

Supplementary information Experimental details and supporting data are available in the online version of the paper.

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Zhao, H., Guo, Y., Yuan, A. et al. Nature-inspired nanothylakoids for multimodal cancer therapeutics. Sci. China Mater. 65, 1971–1979 (2022). https://doi.org/10.1007/s40843-021-2003-5

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  • DOI: https://doi.org/10.1007/s40843-021-2003-5

Keywords

  • nanothylakoids
  • multimodality
  • therapeutics