2. Academic Validation
  3. Slimming and Reinvigorating Tumor-Associated Dendritic Cells with Hierarchical Lipid Rewiring Nanoparticles

Slimming and Reinvigorating Tumor-Associated Dendritic Cells with Hierarchical Lipid Rewiring Nanoparticles

  • Adv Mater. 2023 Apr 25;e2211415. doi: 10.1002/adma.202211415.
Chunchen Xu 1,  Xiaoyuan Ji 1,  Yanfeng Zhou 1,  Yuchun Cheng 2,  Daoxia Guo 1,  Qian Li 3,  Nan Chen 2,  Chunhai Fan 3,  Haiyun Song 1
Affiliations

Affiliations

  • 1 State Key Laboratory of Oncogenes and Related Genes, Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
  • 2 College of Chemistry and Materials Science, The Education Ministry Key Lab of Resource Chemistry, Joint International Research Laboratory of Resource Chemistry of Ministry of Education, Shanghai Key Laboratory of Rare Earth Functional Materials, and Shanghai Frontiers Science Center of Biomimetic Catalysis, Shanghai Normal University, Shanghai, 200234, China.
  • 3 School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules and National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai, 200240, China.
PMID: 37096955 DOI: 10.1002/adma.202211415
Abstract

Dendritic cells (DCs) are crucial mediators of innate and adaptive anti-tumor immunity, whereas exogenously- and endogenously-driven lipid accumulation causes immune tolerance of tumor-associated DCs (TADCs) and thereby diminishes tumor responsiveness to various therapies. Herein, we design a type of multilevel lipid rewiring nanoparticles (NPs) for TADC revitalization. These self-assembled NPs specifically bind to the lipid transport receptor Msr1 on the TADC surface and orchestrate the restriction of extracellular lipid uptake, cytoplasmic de novo lipid biosynthesis and nuclear lipogenic gene transcription. We find that the slimming of TADCs via the three-in-one lipid metabolic reprogramming substantially promotes their maturation and rehabilitate their functions in inflammatory cytokine production, cytotoxic T cell recruitment and tumor inhibition. Significantly, it further overcomes tumor resistance to immune checkpoint blockade therapy. Our study presents a non-canonical strategy to remodel tumor-infiltrating immune cells and paves a new path for improving the efficacy of Cancer Immunotherapy. This article is protected by copyright. All rights reserved.

Keywords

cancer therapy; dendritic cells; immune cell remodeling; immune tolerance; lipid rewiring nanoparticles.

Figures
Products