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pH-gated nanoparticles selectively regulate lysosomal function of tumour-associated macrophages for cancer immunotherapy

Author

Listed:
  • Mingmei Tang

    (Peking University
    Peking University)

  • Binlong Chen

    (Peking University)

  • Heming Xia

    (Peking University)

  • Meijie Pan

    (Peking University)

  • Ruiyang Zhao

    (Peking University)

  • Jiayi Zhou

    (Peking University)

  • Qingqing Yin

    (Peking University)

  • Fangjie Wan

    (Peking University)

  • Yue Yan

    (Peking University)

  • Chuanxun Fu

    (Peking University)

  • Lijun Zhong

    (Peking University Health Science Center)

  • Qiang Zhang

    (Peking University
    Peking University)

  • Yiguang Wang

    (Peking University
    Peking University
    Peking University)

Abstract

Tumour-associated macrophages (TAMs), as one of the most abundant tumour-infiltrating immune cells, play a pivotal role in tumour antigen clearance and immune suppression. M2-like TAMs present a heightened lysosomal acidity and protease activity, limiting an effective antigen cross-presentation. How to selectively reprogram M2-like TAMs to reinvigorate anti-tumour immune responses is challenging. Here, we report a pH-gated nanoadjuvant (PGN) that selectively targets the lysosomes of M2-like TAMs in tumours rather than the corresponding organelles from macrophages in healthy tissues. Enabled by the PGN nanotechnology, M2-like TAMs are specifically switched to a M1-like phenotype with attenuated lysosomal acidity and cathepsin activity for improved antigen cross-presentation, thus eliciting adaptive immune response and sustained tumour regression in tumour-bearing female mice. Our findings provide insights into how to specifically regulate lysosomal function of TAMs for efficient cancer immunotherapy.

Suggested Citation

  • Mingmei Tang & Binlong Chen & Heming Xia & Meijie Pan & Ruiyang Zhao & Jiayi Zhou & Qingqing Yin & Fangjie Wan & Yue Yan & Chuanxun Fu & Lijun Zhong & Qiang Zhang & Yiguang Wang, 2023. "pH-gated nanoparticles selectively regulate lysosomal function of tumour-associated macrophages for cancer immunotherapy," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41592-0
    DOI: 10.1038/s41467-023-41592-0
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    References listed on IDEAS

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    1. Katherine A. Michaelis & Mason A. Norgard & Xinxia Zhu & Peter R. Levasseur & Shamilene Sivagnanam & Shannon M. Liudahl & Kevin G. Burfeind & Brennan Olson & Katherine R. Pelz & Diana M. Angeles Ramos, 2019. "The TLR7/8 agonist R848 remodels tumor and host responses to promote survival in pancreatic cancer," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    2. Qingqing Yin & Anni Pan & Binlong Chen & Zenghui Wang & Mingmei Tang & Yue Yan & Yaoqi Wang & Heming Xia & Wei Chen & Hongliang Du & Meifang Chen & Chuanxun Fu & Yanni Wang & Xia Yuan & Zhihao Lu & Qi, 2021. "Quantitative imaging of intracellular nanoparticle exposure enables prediction of nanotherapeutic efficacy," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
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