Targeting the SOX9/TIMP1 Axis with iRGD-Conjugated Nanoplatform Enhances Dendritic Cell Function and Photodynamic Immunotherapy in Gastric Cancer.

ABSTRACT: Gastric cancer (GC) remains a therapeutic challenge due to its immunosuppressive microenvironment. This study reveals that the SOX9/TIMP1/FAK/PI3K axis impedes dendritic cell (DC) maturation and antitumor immunity in GC, using integrated single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST-seq) analysis. Irgd-conjugated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) co-loaded with small interfering RNA targeting SOX9 (si-SOX9), the photosensitizer chlorin e6 (Ce6), and L-arginine (L-Arg) (termed iRGD NPs@si-SOX9/CL) are developed to simultaneously disrupt this immunosuppressive axis and amplify photodynamic therapy (PDT). In vitro, these NPs enhance cellular uptake and lysosomal escape, suppressing SOX9 expression and generating reactive oxygen species (ROS) and

SUBMITTER: Zhong B 

PROVIDER: S-EPMC12806509 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature