pH-gated nanoparticles selectively regulate lysosomal function of tumour-associated macrophages for cancer immunotherapy
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-presenta...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-09-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-41592-0 |
| _version_ | 1797558232630165504 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Mingmei Tang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T17:28:27Z |
| format | Article |
| id | doaj.art-6a88b16abb1246a7b88f73f8cb9119d6 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-10T17:28:27Z |
| publishDate | 2023-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-6a88b16abb1246a7b88f73f8cb9119d62023-11-20T10:06:32ZengNature PortfolioNature Communications2041-17232023-09-0114111610.1038/s41467-023-41592-0pH-gated nanoparticles selectively regulate lysosomal function of tumour-associated macrophages for cancer immunotherapyMingmei Tang0Binlong Chen1Heming Xia2Meijie Pan3Ruiyang Zhao4Jiayi Zhou5Qingqing Yin6Fangjie Wan7Yue Yan8Chuanxun Fu9Lijun Zhong10Qiang Zhang11Yiguang Wang12State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking UniversityBeijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery System, School of Pharmaceutical Sciences, Peking UniversityBeijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery System, School of Pharmaceutical Sciences, Peking UniversityBeijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery System, School of Pharmaceutical Sciences, Peking UniversityBeijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery System, School of Pharmaceutical Sciences, Peking UniversityBeijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery System, School of Pharmaceutical Sciences, Peking UniversityBeijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery System, School of Pharmaceutical Sciences, Peking UniversityBeijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery System, School of Pharmaceutical Sciences, Peking UniversityBeijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery System, School of Pharmaceutical Sciences, Peking UniversityBeijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery System, School of Pharmaceutical Sciences, Peking UniversityCenter of Medical and Health Analysis, Peking University Health Science CenterState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking UniversityState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking UniversityAbstract 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.https://doi.org/10.1038/s41467-023-41592-0 |
| spellingShingle | 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 pH-gated nanoparticles selectively regulate lysosomal function of tumour-associated macrophages for cancer immunotherapy Nature Communications |
| title | pH-gated nanoparticles selectively regulate lysosomal function of tumour-associated macrophages for cancer immunotherapy |
| title_full | pH-gated nanoparticles selectively regulate lysosomal function of tumour-associated macrophages for cancer immunotherapy |
| title_fullStr | pH-gated nanoparticles selectively regulate lysosomal function of tumour-associated macrophages for cancer immunotherapy |
| title_full_unstemmed | pH-gated nanoparticles selectively regulate lysosomal function of tumour-associated macrophages for cancer immunotherapy |
| title_short | pH-gated nanoparticles selectively regulate lysosomal function of tumour-associated macrophages for cancer immunotherapy |
| title_sort | ph gated nanoparticles selectively regulate lysosomal function of tumour associated macrophages for cancer immunotherapy |
| url | https://doi.org/10.1038/s41467-023-41592-0 |
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