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Programmable starving-photodynamic synergistic cancer therapy

程序化饥饿与光动力协同癌症治疗研究

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Abstract

Synergistic therapy combines multiple therapeutic approaches in one shot, thus could significantly amplify the therapeutic effects. However, how to design the desirable combination to maximize the synergistic effect is still a big challenge in cancer management. Herein, a nano-agent composed of glucose oxidase (GOx) and upconversion nanoparticles (UCNPs) were constructed for programmable starving-photodynamic synergistic cancer therapy through cascade glucose oxidation and hydrogen peroxide photolysis. In this nanoagent, GOx modulated the tumor glucose metabolism and consumed the β-D-glucose to produce H2O2. The glucose depletion induced “starvation” in cancer cells and caused cell death. Afterwards, the generated H2O2 was photolyzed by the invisible ultraviolet emission of UCNPs under near-infrared light excitation at 980 nm. The toxic hydroxyl radicals produced by photolysis further induced cancer cell death. Both in vitro and in vivo experiments confirmed that this starving-photodynamic synergistic therapy significantly outran any single therapy. This study paves an avenue to design programmable starving-photodynamic synergistic therapy for cancer management.

摘要

协同治疗是指将多种治疗方法联合在一起使用, 从而显著增强治疗效果. 然而, 如何设计出理想的组合以最大限度地发挥协同效应仍是肿瘤治疗的一大挑战. 在此, 我们构建了一种由葡萄糖氧化酶修饰的上转换纳米制剂, 用于程序化的肿瘤饥饿-光动力协同治疗研究. 葡萄糖氧化酶催化氧化肿瘤内的葡萄糖并产生过氧化氢, 该过程消耗葡萄糖和氧气, 使得肿瘤细胞缺乏营养物质处于“饥饿”状态, 导致细胞死亡. 并且在980 nm的近红外光激发下, 上转换纳米颗粒激发产生紫外可见光, 将双氧水裂解成毒性更强的羟基自由基, 进一步杀死肿瘤细胞. 体外和体内实验均证实这种饥饿-光动力协同治疗明显优于任何单一治疗. 本研究为设计程序可控的饥饿-光动力协同治疗提供了理论支撑.

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Acknowledgements

This work was financially supported by the National Natural Science Foundation of China (21807073, 31771036 and 51703132), the Basic Research Program of Shenzhen (JCYJ20170818144745087, JCYJ20180507182413022 and JCYJ20170412111100742), Guangdong Province Natural Science Foundation of Major Basic Research and Cultivation Project (2018B030308003), Fok Ying-Tong Education Foundation for Young Teachers in the Higher Education Institutions of China (161032), and China Postdoctoral Science Foundation (2018M630987 and 2019T120752). We thank Instrumental Analysis Center of Shenzhen University (Lihu Campus).

Author information

Zeng L, Huang K and Huang P conceived the idea, proposed the strategy, performed the experiments and wrote the manuscript. Wan Y, Zhang J, and Jiang C performed the cell and animal experiments. Yao X and Lin J helped writing and modifying the manuscript. Huang P supervised the study, designed the project, evaluated the data and wrote the manuscript.

Correspondence to Peng Huang 黄鹏.

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Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary information

Supporting data are available in the online version of the paper.

Leli Zeng received his PhD degree from Sun Yat-Sen University in 2017. During 2016–2017, he conducted a one-year study at St. John’s University as a visiting scholar. In 2017–2019, he came to Shenzhen University as a postdoctoral fellow. Now he works in the Seventh Affiliated Hospital, Sun Yat-sen University as a distinguished associate research fellow. His current research interest is focused on organic molecular probe, metal-based anticancer complexes and nanomaterials for molecular detection and cancer therapy.

Peng Huang is a distinguished professor, Chief of the Laboratory of Evolutionary Theranostics (LET), and director of the Department of Molecular Imaging, at the School of Biomedical Engineering, Shenzhen University Health Science Center, China. He received his PhD degree in Biomedical Engineering from Shanghai Jiao Tong University in 2012. He then joined the Laboratory of Molecular Imaging and Nanomedicine (LOMIN) at the National Institutes of Health (NIH) as a postdoctoral fellow. In 2015, he moved to Shenzhen University as a distinguished professor. His research focuses on the design, syntheses, and biomedical applications of multifunctional nanomaterials. Starting from 2008, Dr. Huang has authored over 170 peer-reviewed papers, which have received total citations of >11,000 times and given him an H-index of 58.

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Zeng, L., Huang, K., Wan, Y. et al. Programmable starving-photodynamic synergistic cancer therapy. Sci. China Mater. (2020) doi:10.1007/s40843-019-1226-8

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Keywords

  • upconversion nanoparticles
  • starvation therapy
  • photodynamic therapy
  • synergistic cancer therapy