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

Mingmei Tang, Binlong Chen, Heming Xia, Meijie Pan, Ruiyang Zhao, Jiayi Zhou, Qingqing Yin, Fangjie Wan, Yue Yan, Chuanxun Fu, Lijun Zhong, Qiang Zhang and Yiguang Wang ()
Additional contact information
Mingmei Tang: 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
Yiguang Wang: Peking University

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: 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.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-41592-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41592-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-41592-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().