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Nanovesicles loaded with a TGF-β receptor 1 inhibitor overcome immune resistance to potentiate cancer immunotherapy

Author

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  • Mengxue Zhou

    (Chinese Academy of Sciences)

  • Jiaxin Wang

    (Chinese Academy of Sciences
    Inner Mongolia University)

  • Jiaxing Pan

    (Chinese Academy of Sciences)

  • Hui Wang

    (Inner Mongolia University)

  • Lujia Huang

    (Chinese Academy of Sciences)

  • Bo Hou

    (Chinese Academy of Sciences)

  • Yi Lai

    (Chinese Academy of Sciences)

  • Fengyang Wang

    (Tongji University School of Medicine)

  • Qingxiang Guan

    (Jilin University)

  • Feng Wang

    (Fudan University)

  • Zhiai Xu

    (East China Normal University)

  • Haijun Yu

    (Chinese Academy of Sciences)

Abstract

The immune-excluded tumors (IETs) show limited response to current immunotherapy due to intrinsic and adaptive immune resistance. In this study, it is identified that inhibition of transforming growth factor-β (TGF-β) receptor 1 can relieve tumor fibrosis, thus facilitating the recruitment of tumor-infiltrating T lymphocytes. Subsequently, a nanovesicle is constructed for tumor-specific co-delivery of a TGF-β inhibitor (LY2157299, LY) and the photosensitizer pyropheophorbide a (PPa). The LY-loaded nanovesicles suppress tumor fibrosis to promote intratumoral infiltration of T lymphocytes. Furthermore, PPa chelated with gadolinium ion is capable of fluorescence, photoacoustic and magnetic resonance triple-modal imaging-guided photodynamic therapy, to induce immunogenic death of tumor cells and elicit antitumor immunity in preclinical cancer models in female mice. These nanovesicles are further armored with a lipophilic prodrug of the bromodomain-containing protein 4 inhibitor (i.e., JQ1) to abolish programmed death ligand 1 expression of tumor cells and overcome adaptive immune resistance. This study may pave the way for nanomedicine-based immunotherapy of the IETs.

Suggested Citation

  • Mengxue Zhou & Jiaxin Wang & Jiaxing Pan & Hui Wang & Lujia Huang & Bo Hou & Yi Lai & Fengyang Wang & Qingxiang Guan & Feng Wang & Zhiai Xu & Haijun Yu, 2023. "Nanovesicles loaded with a TGF-β receptor 1 inhibitor overcome immune resistance to potentiate cancer immunotherapy," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39035-x
    DOI: 10.1038/s41467-023-39035-x
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