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DSPE-PEG2000-methotrexate nanoparticles encapsulating phenobarbital sodium kill cancer cells by inducing pyroptosis

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Abstract

Cancer is a life-threatening disease worldwide. Nanomedicine and nanodelivery systems are recently developed scientific field that employs specific materials in the nanoscale range to deliver drugs. Lipid-based nanoparticles are an ideal delivery system since they exhibit many advantages, including high bioavailability, self-assembly, formulation simplicity, and the ability to exhibit a plethora of physicochemical properties. Herein, we report that phenobarbital sodium can kill cancer cells by using the DSPE-PEG2000-methotrexate nanoparticle delivery system, which can target folate receptors that are usually overexpressed on a variety of cancer cells. The released phenobarbital then executes cancer cells by inducing pyroptosis. Results from our animal model further indicate that the nanomedicine of nanoparticle-encapsulated phenobarbital sodium is a promising anticancer therapy.

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Acknowledgements

We thank the support of the animal facility and high-resolution core from Xiamen University.

Funding

This work was supported by grants from the National Natural Science Foundation of China (81971505), Xiamen Medical and Health Guiding Project (3502720224ZD1222), Xiamen City Health Guidance Project (3502Z20224ZD1222), Xiamen Science and Technology Plan Project (3502Z20224026), and Xiamen City Health Guidance Project (3502Z20224ZD1225).

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Author notes

  1. Fengyue Yin and Xiao Xu contributed equally to this work.

Authors and Affiliations

  1. Department of Emergency, Women and Children’s Hospital, School of Medicine, Xiamen University, Xiamen, 361005, China

    Fengyue Yin & Jinling Wang

  2. Department of Pharmacy, Medical College of Guangxi University, Nanning, 530004, Guangxi, China

    Fengyue Yin, Xiao Xu & Roumei Ye

  3. Peking University Health Science Center, Beijing, 100191, China

    Julia Qi

  4. Department of Emergency, Zhongshan Hospital of Xiamen University, Xiamen, 361005, Fujian, China

    Mengyu Guo

  5. Department of Biomedical Engineering, Medical College of Guangxi University, Nanning, 530004, Guangxi, China

    Yubo Wang

  6. Department of Internal Medicine, School of Clinical Medicine, Jiamusi University, Heilongjiang 154007, Jiamusi, China

    Yun Wang

  7. Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen, 361005, Fujian, China

    Qian Lin & Xuan Zhu

  8. Department of Clinical Sciences, Lund University, 21428, Malmö, Sweden

    Daowei Yang

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Contributions

F. Y and X. X performed most of the experiments with the help of other authors. D. Y, X. Z and J. W designed and instructed this study. X. Z and J. W acquired the grants support for this project. D. Y, F. Y and X. X drafted this manuscript, D. Y edited and refined this manuscript. D. Y supervised the manuscript preparation and submission. All authors discussed the results and commented on the manuscript.

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Correspondence to Daowei Yang, Xuan Zhu or Jinling Wang.

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Animal experiments were conducted with the permission of the Xiamen University animal committee. Ethics approval and consent to participate involving human material are not applicable.

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Yin, F., Xu, X., Qi, J. et al. DSPE-PEG2000-methotrexate nanoparticles encapsulating phenobarbital sodium kill cancer cells by inducing pyroptosis. J Mol Med 102, 213–229 (2024). https://doi.org/10.1007/s00109-023-02403-7

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