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Bacterial outer membrane vesicle based versatile nanosystem boosts the efferocytosis blockade triggered tumor-specific immunity

Author

Listed:
  • Wan-Ru Zhuang

    (Beijing Institute of Technology)

  • Yunfeng Wang

    (Beijing Institute of Technology)

  • Weidong Nie

    (Beijing Institute of Technology)

  • Yao Lei

    (Beijing Institute of Technology)

  • Chao Liang

    (Beijing Institute of Technology)

  • Jiaqi He

    (Beijing Institute of Technology)

  • Liping Zuo

    (Beijing Institute of Technology)

  • Li-Li Huang

    (Beijing Institute of Technology)

  • Hai-Yan Xie

    (Beijing Institute of Technology)

Abstract

Efferocytosis inhibition is emerging as an attractive strategy for antitumor immune therapy because of the subsequent leak of abundant immunogenic contents. However, the practical efficacy is seriously impeded by the immunosuppressive tumor microenvironments. Here, we construct a versatile nanosystem that can not only inhibit the efferocytosis but also boost the following antitumor immunity. MerTK inhibitor UNC2025 is loaded into the bacterial outer membrane vesicles (OMVs), which are then modified with maleimide (mU@OMVs). The prepared mU@OMVs effectively inhibits the efferocytosis by promoting the uptake while preventing the MerTK phosphorylation of tumor associated macrophages, and then captures the released antigens through forming universal thioether bonds. The obtained in situ vaccine effectively transfers to lymph nodes by virtue of the intrinsic features of OMVs, and then provokes intense immune responses that can efficiently prevent the growth, metastasis and recurrence of tumors in mice, providing a generalizable strategy for cancer immunotherapy.

Suggested Citation

  • Wan-Ru Zhuang & Yunfeng Wang & Weidong Nie & Yao Lei & Chao Liang & Jiaqi He & Liping Zuo & Li-Li Huang & Hai-Yan Xie, 2023. "Bacterial outer membrane vesicle based versatile nanosystem boosts the efferocytosis blockade triggered tumor-specific immunity," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37369-0
    DOI: 10.1038/s41467-023-37369-0
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    References listed on IDEAS

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    1. Xiang Yu & Yanfeng Dai & Yifan Zhao & Shuhong Qi & Lei Liu & Lisen Lu & Qingming Luo & Zhihong Zhang, 2020. "Melittin-lipid nanoparticles target to lymph nodes and elicit a systemic anti-tumor immune response," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    2. Oh Youn Kim & Hyun Taek Park & Nhung Thi Hong Dinh & Seng Jin Choi & Jaewook Lee & Ji Hyun Kim & Seung-Woo Lee & Yong Song Gho, 2017. "Bacterial outer membrane vesicles suppress tumor by interferon-γ-mediated antitumor response," Nature Communications, Nature, vol. 8(1), pages 1-9, December.
    3. Tingting Wang & Dangge Wang & Haijun Yu & Bing Feng & Fangyuan Zhou & Hanwu Zhang & Lei Zhou & Shi Jiao & Yaping Li, 2018. "A cancer vaccine-mediated postoperative immunotherapy for recurrent and metastatic tumors," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    4. Paola Scaffidi & Tom Misteli & Marco E. Bianchi, 2002. "Release of chromatin protein HMGB1 by necrotic cells triggers inflammation," Nature, Nature, vol. 418(6894), pages 191-195, July.
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