Platelet membrane biomimetic nanomedicine induces dual glutathione consumption for enhancing cancer radioimmunotherapy

Xiaopeng Li; Yang Zhong; Pengyuan Qi; Daoming Zhu; Chenglong Sun; Nan Wei; Yang Zhang; Zhanggui Wang

doi:10.1016/j.jpha.2024.01.003

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Xiaopeng Li, Yang Zhong, Pengyuan Qi, Daoming Zhu, Chenglong Sun, Nan Wei, Yang Zhang, Zhanggui Wang. Platelet membrane biomimetic nanomedicine induces dual glutathione consumption for enhancing cancer radioimmunotherapy[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2024.01.003

Citation:

Xiaopeng Li, Yang Zhong, Pengyuan Qi, Daoming Zhu, Chenglong Sun, Nan Wei, Yang Zhang, Zhanggui Wang. Platelet membrane biomimetic nanomedicine induces dual glutathione consumption for enhancing cancer radioimmunotherapy[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2024.01.003

Citation:

Xiaopeng Li, Yang Zhong, Pengyuan Qi, Daoming Zhu, Chenglong Sun, Nan Wei, Yang Zhang, Zhanggui Wang. Platelet membrane biomimetic nanomedicine induces dual glutathione consumption for enhancing cancer radioimmunotherapy[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2024.01.003

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Platelet membrane biomimetic nanomedicine induces dual glutathione consumption for enhancing cancer radioimmunotherapy

doi: 10.1016/j.jpha.2024.01.003

1 Department of Radiation Oncology, Anhui No. 2 Provincial People’s Hospital, Hefei, China.
2 Department of Electronic Science and Technology, School of Physics and Technology, Wuhan University, Wuhan 430072, China.
3 Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China

Funds:

This work was supported by grants from the the Clinical Science Foundation of Anhui Medical University(2021xkj240).

Received Date: Oct. 15, 2023
Accepted Date: Jan. 04, 2024
Rev Recd Date: Dec. 26, 2023
Available Online: Jan. 18, 2024

Abstract

Abstract

Radiotherapy (RT) is one of the most common treatments for cancer. However, intracellular glutathione (GSH) plays a key role in protecting cancer from radiation damage. Herein, we have developed a platelet membrane biomimetic nanomedicine (PMD) that induces double GSH consumption to enhance tumor radioimmunotherapy. This biomimetic nanomedicine consists of an external platelet membrane and internal organic mesoporous silica nanoparticles (MON) loaded with 2-deoxy-D-glucose (2-DG). Thanks to the tumor-targeting ability of the platelet membranes, PMD can target and aggregate to the tumor site, which is internalized by tumor cells. Within tumor cells overexpressing GSH, MON reacts with GSH to degrade and release 2-DG. This step initially depletes the intracellular GSH content. The subsequent release of 2-DG inhibits glycolysis and adenosine triphosphate (ATP) production, ultimately leading to secondary GSH consumption. This nanodrug combines dual GSH depletion, starvation therapy, and RT to promote immunogenic cell death and stimulate the systemic immune response. In the bilateral tumor model in vivo, distal tumor growth was also well suppressed. The proportion of mature dendritic cells (DC) and CD8+T cells in the mice was increased. This indicates that PMD can promote anti-tumor radioimmunotherapy and has good prospects for clinical application.
- Dual GSH consumption,
- Cancer radioimmunotherapy,
- Platelet membrane biomimetic nanomedicine,
- Starvation therapy,
- organic mesoporous silica nanoparticles

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References(20)

References

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