CXCL12-targeting siRNA nanoparticles alleviate immunosuppression and inhibit tumor progression in esophageal squamous cell carcinoma.

ABSTRACT: Esophageal squamous cell carcinoma (ESCC) is associated with a highly immunosuppressive tumor microenvironment (TME), driven in part by cancer-associated fibroblasts (CAFs) that promote immune evasion through the secretion of CXCL12. CXCL12 interacts with the CXCR4 receptor on immune cells, disrupting CD8⁺ T cell migration and anti-tumor function. To address this, we developed an innovative siRNA-based therapeutic approach targeting CXCL12 in CAFs. Using lipid nanocarriers (LNCs) as delivery vehicles, we engineered LNCs@si-CXCL12 nanoparticles to specifically silence CXCL12 expression in CAFs. In vitro studies demonstrated that LNCs@si-CXCL12 restored CD8⁺ T cell migration and inhibited ESCC cell proliferation and migration. In vivo experiments in a spontaneous ESCC m

SUBMITTER: Zhang S 

PROVIDER: S-EPMC12269133 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature