Injectable Immunotherapeutic Hydrogel Containing RNA-Loaded Lipid Nanoparticles Reshapes Tumor Microenvironment for Pancreatic Cancer Therapy.

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.

• Authors: Chao Gao, Keman Cheng, Yao Li, Ruining Gong, Xiao Zhao, Guangjun Nie, He Ren
• Journal: Nano letters (Nano Lett) Vol. 22 Issue 22 Pg. 8801-8809 (11 23 2022) ISSN: 1530-6992 [Electronic] United States
• PMID: 36251255 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Lipid Nanoparticles
• Hydrogels
• RNA, Small Interfering
• Immunologic Factors
• Interferon Regulatory Factors

Topics

• Humans
• Tumor Microenvironment
• Hydrogels
• Nanoparticles
• Immunotherapy
• RNA, Small Interfering (genetics, therapeutic use)
• Pancreatic Neoplasms (drug therapy)
• Immunologic Factors
• Interferon Regulatory Factors
• Pancreatic Neoplasms