Abstract
Pancreatic cancer immunotherapy is becoming a promising strategy for improving the survival rate of postsurgical patients. However, the low response rate to immunotherapy suggests a low number of antigen-specific T cells and a high number of immunosuppressive tumor-associated macrophages in the pancreatic tumor microenvironment. Herein, we developed an in situ injectable thermosensitive chitosan hydrogel loaded with lipid-immune regulatory factor 5 (IRF5) mRNA/C-C chemokine ligand 5 (CCL5) siRNA (LPR) nanoparticle complexes (LPR@CHG) that reprogram the antitumoral immune niche. The LPR@CHG hydrogel upregulates IRF5 and downregulates CCL5 secretion, which contribute to a significant increase in M1 phenotype macrophages. Tumor growth is controlled by effective M1 phenotype macrophage that initiate T cell-mediated immune responses. Overall, the LPR@CHG hydrogel is expected to be a meaningful immunotherapy platform that can reshape the immunosuppressive tumor microenvironment and improve the efficacy of current pancreatic immunotherapies while minimizing systemic toxicity.
Original language | English (US) |
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Pages (from-to) | 8801-8809 |
Number of pages | 9 |
Journal | Nano Letters |
Volume | 22 |
Issue number | 22 |
DOIs | |
State | Published - Nov 23 2022 |
Keywords
- chitosan hydrogel
- immune therapy
- liposome nanoparticles
- RNA delivery
- TAMs
ASJC Scopus subject areas
- Bioengineering
- Chemistry(all)
- Materials Science(all)
- Condensed Matter Physics
- Mechanical Engineering