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Programmable starving-photodynamic synergistic cancer therapy

  • Leli Zeng (曾乐立)
  • Kai Huang (黄凯)
  • Yilin Wan (万艺林)
  • Jing Zhang (张景)
  • Xikuang Yao (姚锡矿)
  • Chao Jiang (蒋超)
  • Jing Lin (林静)
  • Peng Huang (黄鹏)Email author
Articles
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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.

Keywords

upconversion nanoparticles starvation therapy photodynamic therapy synergistic cancer therapy 

程序化饥饿与光动力协同癌症治疗研究

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.

Notes

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 contributions

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.

Supplementary material

40843_2019_1226_MOESM1_ESM.pdf (2.3 mb)
Programmable starving-photodynamic synergistic cancer therapy

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Copyright information

© Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature 2020

Authors and Affiliations

  • Leli Zeng (曾乐立)
    • 1
    • 2
  • Kai Huang (黄凯)
    • 1
  • Yilin Wan (万艺林)
    • 1
  • Jing Zhang (张景)
    • 1
  • Xikuang Yao (姚锡矿)
    • 1
  • Chao Jiang (蒋超)
    • 1
  • Jing Lin (林静)
    • 1
  • Peng Huang (黄鹏)
    • 1
    Email author
  1. 1.Marshall Laboratory of Biomedical EngineeringInternational Cancer Center, Laboratory of Evolutionary Theranostics (LET), School of Biomedical Engineering, Shenzhen University Health Science CenterShenzhenChina
  2. 2.Research Centre, The Seventh Affiliated HospitalSun Yat-sen UniversityShenzhenChina

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